Faculty Bibliography

A variety of therapeutic modalities are available to alter the abnormalities seen in patients with chronic kidney disease (CKD). A comprehensive plan can now be developed to slow the progression of CKD. Two clinical cases of delay in the need for renal replacement therapy are described. This delay was achieved by using recognized recommendations for optimal diabetes therapy (HbA1c target 7 %), goals for blood pressure levels, reduction of proteinuria, and the proper use of ACEI/ARB therapies. Recent recommendations include BP <140/90 mmHg for patients <60 years old and <150/90 mmHg for older patients unless they have CKD or diabetes. Limits on dietary sodium and protein intake and body weight reduction will decrease proteinuria. Proper treatment for elevated serum phosphorous and parathyroid hormone levels is now appreciated as well as the benefits of therapy for dyslipidemias and anemia. Concerns regarding unfavorable outcomes with excess ESA therapy have led to hemoglobin goals in the 10-12 g/dL range. Finally, new therapeutic considerations for the treatment of acidosis and hyperuricemia are presented with data available to suggest that increasing serum bicarbonate to >22 mmol/L is beneficial, while serum uric acid therapeutic goals are still uncertain. Also, two as yet insufficiently understood approaches to altering the course of CKD (FGF-23 level reduction and balancing gut microbiota) are noted.

PURPOSE: Hypernatremia is a common electrolyte disorder associated with adverse outcomes such as increased length of stay and mortality due to a variety of factors. Our aim was to investigate known factors as well as other variables which we had identified in hospitalized hypernatremic geriatric patients and their relationship to patient outcomes. METHODS: A retrospective chart review of all adult hospitalized patients in a 4-month period with a serum sodium level >150 mmol/L was performed. Factors evaluated included use of a nephrology consultation, certain urine laboratory measures, fluids employed, rate of correction, and patient's level of care setting. Outcome measures included length of stay and mortality. RESULTS: The patient mortality rate was 52 %. Mean age was 79.6 years (n = 33), and mean initial sodium level was 152.6 mmol/L. Plasma and urine osmolality, and urine sodium concentration were checked in less than 25 % of patients. Fifteen of 18 patients in the ICU expired, whereas only 2 of 15 patients not in the ICU expired (p < 0.0004, OR 32.50, CI 95 % (4.68-225.54)). Of the 23 patients (70 %) who had their serum sodium level corrected, 11 were corrected in 3 days, but this difference did not affect mortality rate (45 vs. 50 %, p = 0.99). The mortality rate was similar (60 %, p = 0.52) for those whose serum sodium level never corrected suggesting that correction did not influence outcomes. The fluids chosen for therapy of the hypernatremia were appropriate to the patients volume status. Five of 15 patients who received a nephrology consultation survived, while 11 of 18 patients without a nephrology consultation survived (p = 0.12). The mean length of stay was 25.0 +/- 23.9 days and no different for those who expired versus those who survived (25.2 +/- 21.2 vs. 24.8 +/- 25.9 days, p = 0.96). CONCLUSIONS: Hypernatremia is associated with a poor prognosis, and outcomes are still disappointing despite appropriate rates of correction, intensive monitoring, and the involvement of a nephrologist. Strategies directed at avoidance of the development of hypernatremia and attention to concomitant disease may provide significant patient benefit.

Neurofibromatosis type 1 (NF-1), also known as von Recklinghausen's disease, is an autosomal dominant genetic disorder. NF-I vasculopathy has been used to describe various vascular malformations associated with NF-1. Secondary hypertension related to NF-1 vasculopathy has been reported because of renal artery stenosis, coarctation of the abdominal aorta and other vascular lesions; however, coarctation of the thoracic aorta has seldom been reported. We report the first case, to our knowledge, of isolated coarctation of thoracic aorta in a pregnant female with NF-1. Healthcare providers caring for patients with NF-1 should be aware of associated vascular complications.

A 57-year-old man with chronic kidney disease stage 5 presented for ambulatory evaluation of his arteriovenous fistula. He underwent rheolytic thrombectomy with tissue plasminogen activator infusion, angioplasty, and brachial artery stenting under local sedation. His immediate postoperative course was complicated by hypotension, cardiac dysrhythmias and hyperkalemia requiring emergent hemodialysis, due to severe intravascular hemolysis. This case illustrates that mechanical thrombectomy can cause clinically significant intravascular hemolysis, thus careful postoperative monitoring is recommended.

Elevated troponin T is known to be a prognostic marker for long-term cardiac events and mortality in asymptomatic end-stage renal disease patients. There are conflicting data in this regard with respect to troponin I (TnI). We recently showed a high incidence of elevated TnI levels in asymptomatic hemodialysis (HD) patients using a new generation sensitive TnI assay. The aim of this pilot study was to explore the prognostic value of TnI, as measured with this new assay, as a marker for outcomes in HD patients over a 2-year follow-up period. Fifty-one asymptomatic HD patients were enrolled, and pre-dialysis TnI levels were checked once monthly over 3 consecutive months. Patients were considered to be in the TnI positive group if TnI level on any of the three draws was >/=0.035 ng/ml. All patients were followed for a period of 2 years. The primary end points were acute coronary syndrome, coronary revascularization, sudden death, or cardiac arrest. The secondary end point was all-cause mortality. Elevated TnI levels were found in 51% (26/51) of patients in our cohort. One TnI positive patient was subsequently lost to follow up. There were 6 cardiac events over 2 years, all of which were in the troponin positive group (6/25 or 24%). The presence of a positive TnI at baseline was significantly associated with future cardiac events (p = 0.022). A prior history of coronary artery disease (CAD) was also significantly related to future cardiac events (p = 0.010). No patient with negative TnI at baseline developed a cardiac event, while 45.5% of those with both a positive TnI and a history of CAD had an event. Fourteen deaths occurred over 2 years, 8 in TnI positive and 6 in the negative group. All-cause mortality was not associated with elevated TnI levels at baseline. We found a significant association between positive TnI and subsequent cardiac events in asymptomatic HD patients followed for 2 years. TnI levels, as measured with a sensitive assay, may be useful in assessing cardiac risk in asymptomatic HD patients. This needs further confirmation in a larger cohort.

Tolvaptan, an oral, selective arginine vasopressin (AVP) V2 receptor antagonist has been approved for the treatment of euvolemic and hypervolemic hyponatremia in the United States. This report summarizes our center's experience with thirteen patients treated for hyponatremia with one 15-mg dose of tolvaptan. The patients had euvolemic or hypervolemic hyponatremia with decreased serum osmolality and serum sodium (SNa) levels less than 129 mEq/L. Eight patients had a diagnosis of the syndrome of inappropriate antidiuretic hormone (SIADH), and five patients had a diagnosis of congestive heart failure (CHF). Results revealed an increase in SNa in all patients from 122.5 +/- 4.2 to 128.9 +/- 4.1 mEq/L (P < 0.05). The mean increase in SNa of 6.4 mEq/L (range 2-10 mEq/L) 24 h post-tolvaptan was not different in the two groups of patients, but SIADH patients had higher pre and post-tolvaptan SNa levels than CHF patients. Urine osmolalities (UOsm) decreased in all patients, and the patients with SIADH had significantly higher baseline UOsm and a larger decrease in UOsm 12 h post-tolvaptan administration when compared with the CHF patients. AVP levels did not change post-tolvaptan administration. However, the magnitude of increase in SNa levels was inversely related to pretolvaptan AVP levels in the SIADH subgroup (r = -0.7, P = 0.01). Three SIADH patients received small amounts of D5W to attenuate changes in SNa. No significant changes in mean arterial pressure, serum potassium, serum glucose, and blood urea nitrogen or serum creatinine were observed. The data show that tolvaptan is effective for the treatment of hyponatremia and may produce differing responses in disparate patient groups

ABSTRACT: BACKGROUND: Lanthanum carbonate (FOSRENOL(R)) is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to </=5.5 mg/dL in patients with end-stage renal disease (ESRD) was assessed in a clinical practice setting. METHODS: A 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium x phosphorus product, and parathyroid hormone levels were secondary endpoints. RESULTS: Serum phosphorus control (</=5.5 mg/dL) was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate. CONCLUSIONS: Serum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0016012

BACKGROUND: Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. METHODS: We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. RESULTS: At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (>/=0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. CONCLUSION: Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level

We randomized patients with chronic kidney disease (serum creatinine >/= 1.5 mg/dl or glomerular filtration rate (GFR) <60 ml/min/1.73 m(2)) in a double-blind fashion to receive saline or sodium bicarbonate prior to and after cardiac or vascular angiography. The primary endpoint was contrast-induced nephropathy (CIN), defined as an increase in serum creatinine by 25% or by 0.5 mg/dl from baseline. Patients with congestive heart failure (CHF), cardiac ejection fraction (EF) <30%, or GFR < 20 ml/min/1.73 m(2) were excluded. The study was discontinued (after 142 patients were randomized) due to a low incidence of CIN (1.5%). We retrospectively identified all cases of CIN (n = 30) at our institution during the same time period to see if these patients differed from our trial sample. There was no difference in serum creatinine (1.7 +/- 0.4 vs. 1.7 +/- 0.6 mg/dL), GFR (42.7 +/- 9.7 vs. 45.3 +/- 3.2 ml/min), incidence of diabetes (51.8% vs. 63.3%), contrast volume (121.7 +/- 63.8 vs. 122.7 +/- 68.3 ml), ACE inhibitor or angiotensin receptor blocker use (54.0% vs 63.3%), and periprocedure diuretic use (33.1% vs 26.7%). On multivariate analysis, only a cardiac ejection fraction (EF) of less than 40% was significantly associated with CIN (odds ratio, 4.52; 95% confidence interval, 1.30-15.71; P = 0.02). In all, 22/30 patients (73.3%) who developed CIN had at least one or more characteristics that would have excluded their enrollment in our randomized trial including evidence of congestive heart failure (17/30 patients), EF less than 30% (9 patients), age greater than 85 years (2 patients), or advanced renal failure with a baseline GFR of less than 20 cc/min (1 patient). In summary, patients with CKD without evidence of CHF who receive adequate hydration appear to have a very low risk of CIN associated with angiography. A low EF (less than 40%) appeared to be the most significant risk factor for CIN in our population