Linda Shavit

Effect of eplerenone on blood pressure and the renin-angiotensin-aldosterone system in oligo-anuric chronic hemodialysis patients - a pilot study.

INTRODUCTION AND AIMS Recent studies have suggested that aldosterone has many effects in addition to its ability to cause the kidney to retain sodium. To test the hypothesis that aldosterone can cause hypertension in a manner that does not involve renal sodium retention, we administered eplerenone, a specific aldosterone antagonist, to oligo-anuric chronic hemodialysis patients who had HTN. METHODS 220 chronic hemodialysis patients underwent initial screening. Of these, 8 patients were followed for 8 weeks and their blood pressure, weight, plasma potassium, aldosterone levels and plasma renin activity were recorded. After a 4 week run in period, each patient received eplerenone 25 mg twice daily for another 4 weeks. RESULTS Administration of eplerenone for 4 weeks decreased predialysis systolic blood pressure from 166 ± 14 to 153 ± 10 mmHg (p < 0.05). Eplerenone had no effect on diastolic blood pressure, potassium, predialysis weight, intradialytic weight gain, plasma aldosterone or PRA. CONCLUSION Eplerenone significantly reduces systolic blood pressure in oligo-anuric hypertensive hemodialysis patients without effect on plasma aldosterone concentrations or plasma renin activity. Plasma potassium increases minimally after 4 weeks of therapy, a finding that raises some concern for long-term eplerenone use in chronic hemodialysis.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study

BACKGROUND AND OBJECTIVES Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. RESULTS Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. CONCLUSIONS Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Severe renal failure and microangiopathic hemolysis induced by malignant hypertension--case series and review of literature.

Malignant nephrosclerosis is acute renal failure in the setting of malignant hypertension and may be associated with thrombotic microangiopathy. Although the prognosis has improved considerably over the past decades, renal dysfunction remains an important cause of morbidity and mortality. Adequate control of blood pressure is crucial, allows gradual healing of the necrotizing vascular lesions and may induce stabilization and improvement of renal function in about 50 - 80% of involved patients. In addition, recent investigations have provided a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. We report 3 patients who developed severe acute renal failure requiring dialysis initiation in the setting of malignant hypertension. All patients had kidney biopsy proven malignant nephrosclerosis and presented with symptoms of thrombotic microangiopathy. Despite adequate blood pressure control the prognosis of our patients varied.

Use of Pregabalin in the Management of Chronic Uremic Pruritus

CONTEXT Uremic pruritus (UP) affects many patients suffering from chronic kidney disease (CKD) and has a negative impact on quality of life and survival. It has become increasingly evident that central transmission and sensitization processes similar to those observed in chronic pain are important mechanisms of pruritus. OBJECTIVES To test the potential role of pregabalin in reducing the intensity of UP in CKD patients. METHODS We prospectively collected data on CKD patients who suffered from severe intractable pruritus. Patients were asked to record the intensity of pruritus on a visual analogue scale. RESULTS Twelve patients were studied. The average pretreatment pruritus score was 9.7 ± 0.9 and decreased to 3.7 ± 2.35, 3.2 ± 1.75, and 3 ± 1.5 after one, four, and 24 weeks of treatment, respectively (P < 0.05). The positive effect of pregabalin was demonstrated during the first week of therapy in six patients. Most patients required 25mg a day. Pregabalin was well tolerated, with somnolence and dizziness developing in two patients. CONCLUSION We demonstrated dramatic improvement of long-standing UP after the initiation of pregabalin. We suggest that pregabalin can be used safely in CKD but careful titration of the dose is required to obtain an optimal response and minimize the possible adverse effects.

Metformin As an Addition to Conventional Chemotherapy in Breast Cancer

metformin inbreast cancer may be related to activation of adenosine monophosphate‐activated protein kinase, which may ultimately result in a rapid inhibition of cellular protein synthesis and growth of tumor cells. We suggest, however, that additional mechanisms may play a part. It is a well-accepted fact that chronic inflammation is a major contributory factor to cancer development and progression, and elevated levels of various nonspecific markers of inflammation in the serum have been shown to be associated with poor survival in a number of different cancers. Pierce et al 3 have recently assessed the relationship between circulating levels of C-reactive protein and serum amyloid A and breast cancer survival. They showed that raised levels of these inflammatory markers were associated with a significantly reduced overall survival and a trend toward a reduced diseasefreesurvival.Patientswithtype2diabetesmellitustendtohavehigher C-reactive protein concentrations than those without it, suggesting that inflammation may contribute to the higher risk of breast cancer and worse prognosis of malignant disease in these patients. 4 Thereisevidencetosuggestthatmetforminhasapositiveimpact on inflammation and endothelial dysfunction. Metformin was compared with another oral hypoglycaemic agent, repaglinide, in nonobese patients with type 2 diabetes and shown to be more effective in

Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Complications and Mortality in Patients Undergoing Non-Cardiac Major Surgery

Introduction: We tested the hypothesis that urinary and serum neutrophil gelatinase-associated lipocalins (NGAL) early after non-cardiac major surgery predict postoperative acute kidney injury (AKI), complications and mortality. Methods: We studied 74 patients undergoing orthopedic, vascular and abdominal surgery lasting ≧2 h. NGAL was measured in preoperative, as well as 2- and 6-hour postoperative samples. The primary outcome was AKI. Secondary outcome was postoperative infection and death. Results: 10 patients (13.5%) developed AKI, 19 (26%) reached secondary outcomes, of whom 5 (7%) died. Serum NGAL was significantly higher in patients with diabetes and chronic kidney disease (CKD). No significant correlation was detected between serum or urine NGAL and subsequent development of AKI. Urine NGAL at 6 h and serum NGAL at 2 and 6 h were strongly correlated with postoperative infection and death (p = 0.004, p = 0.013 and p = 0.001, respectively). Conclusions: Our data suggest that in the general surgical population, NGAL could serve as a potent early biomarker for postoperative infection, and that the presence of CKD and diabetes mellitus is associated with higher levels of NGAL and may influence its predictive value.

What is nephrocalcinosis

The available publications on nephrocalcinosis are wide-ranging and have documented multiple causes and associations of macroscopic or radiological nephrocalcinosis, most often located in the renal medulla, with various metabolic and genetic disorders; in fact, so many and various are these that it is difficult to define a common underlying mechanism. We have reviewed nephrocalcinosis in relation to its definition, genetic associations, animal models, and putative mechanisms. We have concluded, and hypothesized, that nephrocalcinosis is primarily a renal interstitial process, resembling metastatic calcification, and that it may have some features in common with, and pathogenic links to, vascular calcification.

Mild hyponatremia is associated with functional and cognitive decline in chronic hemodialysis patients.

BACKGROUND A high incidence and adverse outcomes of cognitive impairment in dialysis patients have recently become recognized. Classical risk factors, uremia, anemia, metabolic disturbances, and hemodynamic instability during dialysis accelerate vascular cognitive impairment. AIMS To evaluate laboratory factors that influence cognitive function in consecutive chronic hemodialysis (CHD) patients over a 2-year period. METHODS Between June 2010 and June 2011 we conducted a prospective, single-center trial that evaluated cognitive function in adult chronic hemodialysis (HD) patients. A battery of cognitive function tests was used: modified mini mental state (3MS), trailmaking tests A (trails A) and B (trails B). The 15-item geriatric depression scale (GDS) and the activities of daily living (ADL) test were used, respectively, for assessing symptoms of depression and global functional status. All tests were performed twice at yearly intervals in consecutive HD patients. Global cognitive impairment was defined as a 3MS < 80 and impaired executive function as a Trails A performance time > 75 seconds and Trails B > 180 seconds. RESULTS 56 chronic HD patients aged 65.00 ± 17.8 years were studied; 57% of them were males. 86% suffered from hypertension (HTN), 40% were diabetics and ~ 1/3 had ischemic heart disease, congestive heart failure (CHF), and dyslipidemia. Average plasma calcium, phosphorus, and PTH were within the recommended range. No features suggestive of malnutrition, severe anemia, inflammation, or inadequate dialysis were detected. 14 patients (24%) had mild chronic hyponatremia (Na ranges 131 - 135 meq/L). Significant disturbances in global cognitive and executive function were detected in the study patients. In 2010, 50% had 3MS < 80, 71% and 91% had severely impaired trails A and B tests (respectively), 54% had symptoms of depression and 50% suffered from impaired ADL. Retesting of the survivors in 2011 revealed increased prevalence of cognitive and functional declines along with worsening depression scoring. Univariate analysis demonstrated significant correlation between cognitive decline and age, female gender, education, poor executive and functional status, inadequate dialysis dose (Kt/V < 1.2, p = 0.023), high plasma phosphorus levels (p > 6 mg/dL, p = 0.034), and hyponatremia (Na < 135 mEq/L, p = 0.001). Multivariate stepwise logistic regression analysis revealed statistically significant associations between hyponatremia and impaired ADL (p = 0.043) and impaired ADL and mortality (p = 0.002). CONCLUSIONS A high prevalence of global cognitive and executive impairment was detected in our hemodialysis cohort. We found an association between mild chronic hyponatremia and impaired functional status. Whether treatments aimed at modifying hyponatremia could mitigate functional decline or mortality remains to be elucidated.

Nonconvulsive status epilepticus in elderly a possible diagnostic pitfall

INTRODUCTION Nonconvulsive status epilepticus (NCSE) is characterized by behavioral and vegetative abnormalities without classical major convulsive movements. A broad variability in clinical presentation makes this condition difficult to recognize and therefore NCSE is often overlooked especially in elderly. AIM To evaluate the prevalence, clinical features, therapeutic approach and outcomes of NCSE. METHODS This study represents prospectively collected data on patients accepted to the general geriatric ward with acute unexplained change in mental, cognitive, or behavioral status or confusion. Typical electroencephalogram (EEG) changes and significant improvement of these abnormalities and their mental status after administration of anticonvulsive therapy were required to establish the diagnosis of NCSE. RESULTS We identified 14 patients (average age 81 ± 7 years) with clinical and EEG changes consistent with NCSE. All patients suffered from significantly altered consciousness: 9 had acute confusion, 1 presented with coma and 4 with stupor. Eleven patients had diffuse and 3 temporal focal EEG abnormalities. All patients received anticonvulsants and had prompt and dramatic improvement in the EEG changes and in their mental status. CONCLUSION We conclude that high index of clinical suspicion along with typical EEG changes are the key tools to obtain diagnosis of NCSE. In our patients, significant mental impairment along with other adverse prognostic factors (advanced age, multiple comorbidities) pointed toward clear benefits from anticonvulsant therapy. Our experience highlights the importance of EEG in the evaluation of abrupt mental or behavioral changes in the elderly population as NCSE is difficult to diagnose but potentially treatable condition.

Brain metastases: a rare initial presentation of prostate cancer

Although brain metastases are common in cancer patients, carcinoma of the prostate rarely metastasizes to the brain. Cerebral metastases as an initial clinical presentation of prostate carcinoma are extremely rare. We report a patient, who presented with confusion and behavioral changes. Cranial magnetic resonance imaging revealed a large right temporal lobe lesion. The pathological diagnosis of the tumor was consistent with metastatic prostate carcinoma. Further evaluation revealed widespread bony metastases by technetium 99 bone scan and high level of prostate-specific antigen.