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The effect of ergocalciferol on uremic pruritus severity: a randomized controlled trial

Shirazian, Shayan; Schanler, Mary; Shastry, Shuba; Dwivedi, Shaunak; Kumar, Maanvi; Rice, Kathleen; Miyawaki, Nobuyuki; Ghosh, Samiran; Fishbane, Steven
OBJECTIVE:Hemodialysis (HD) patients have a high prevalence of pruritus. 25-Hydroxy vitamin D deficiency is common in this population and may play a role in its etiology. Because of this, we studied whether vitamin D2 treatment with ergocalciferol is effective for relief of uremic pruritus severity as measured by pruritus severity surveys. DESIGN, SETTING, AND SUBJECTS/METHODS:In this double-blind, placebo-controlled, randomized trial, the effect of 12 weeks of ergocalciferol administration on uremic pruritus severity was evaluated. INTERVENTION/METHODS:Fifty HD patients randomly received either ergocalciferol 50,000 international units (IU) or placebo once weekly for 12 weeks. MAIN OUTCOME MEASURE/METHODS:Pruritus severity surveys were completed every 2 weeks by all patients starting from baseline until 12 weeks and serve as the main outcome variable. RESULTS:Twenty-five study participants were randomized to ergocalciferol therapy and 25 were randomized to placebo. At baseline, the only significant difference between the two groups was time on dialysis and white blood cell count. Both groups experienced a decrease in pruritus scores from the beginning to the end of study (percent change -38.9% in the treatment group vs. -47.5% in the placebo group). By intention to treat, the treatment × time effect was not statistically significant (F = 0.71, df = (1, 282), P = .34), indicating that the pruritus score was not significantly lower in the treatment group than the placebo group throughout the study. CONCLUSION/CONCLUSIONS:In conclusion, we did not find ergocalciferol to be effective for the treatment of uremic pruritus.
PMID: 23453391
ISSN: 1532-8503
CID: 3534962

Normal fractional urate excretion identifies hyponatremic patients with reset osmostat

Imbriano, Louis J; Ilamathi, Ekambaram; Ali, Nicole M; Miyawaki, Nobuyuki; Maesaka, John K
BACKGROUND: Reset osmostat (RO) occurs in 36% of patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and is not often considered when evaluating hyponatremic patients. Patients with RO are not usually treated, but recent awareness that symptoms are associated with mild hyponatremia creates a therapeutic dilemma. We encountered patients with hyponatremia, hypouricemia and high urine sodium concentration (UNa), who had normal fractional excretion (FE) of urate and excreted dilute urines that were consistent with RO. We decided to test whether a normal FEurate in nonedematous hyponatremia irrespective of UNa or serum urate would identify patients with RO. METHODS: We determined FEurate in nonedematous hyponatremic patients. A diagnosis of RO was made if urine osmolality (Uosm) was <200 mOsm/kg in a random urine. We performed a modified water-loading test in patients with a normal FEurate whose random Uosm was >200 mOsm/kg. RESULTS: All nonedematous hyponatremic patients with FEurate of 4%-11% had RO, as determined by Uosm <200 mOsm/kg on a random urine collection in 8 patients, or after a modified water-loading test in 6 patients. Plasma antidiuretic hormone (ADH) in 4 patients was undetectable at <1 pg/mL during water-loading. Nine patients had baseline concentrated urine, 12 had UNa >20 mmol/L, 9 were hypouricemic, yet all had a normal FEurate. Comorbidities were similar to those reported in RO. CONCLUSIONS: RO, a benign form of SIADH, occurs commonly. A normal FEurate in a nonedematous hyponatremic patient is highly suggestive of RO. Determining FEurate is superior to serum urate. The therapeutic dilemma for RO must be resolved.
PMID: 22307440
ISSN: 1724-6059
CID: 2388762

Hypothesis: an erythropoietin honeymoon phase exists

Fishbane, Steven; Miyawaki, Nobuyuki; Szczech, Lynda A
TREAT was a recently concluded, and well-powered and designed, study of anemia treatment in chronic kidney disease (CKD). Unlike most previous studies of ESA treatment in nondialysis CKD, TREAT was a placebo-controlled trial. The placebo group in TREAT provides a unique long-term view of a conservative approach to anemia management in nondialysis CKD. The course of mean Hgb levels in the placebo group ran counter to expectations, increasing over time. We discuss possible reasons for this, including a new hypothesis that there may be an erythropoietin 'honeymoon phase' similar to that observed in diabetes mellitus. We propose investigation of this phenomenon as it could lead to less expensive and safer approaches to treatment of CKD anemia.
PMID: 20631675
ISSN: 1523-1755
CID: 3534952

Anemia treatment in chronic kidney disease accompanied by diabetes mellitus or congestive heart failure [Comment]

Fishbane, Steven; Miyawaki, Nobuyuki
Anemia is common in chronic kidney disease (CKD). The CHOIR study found increased risk of a composite cardiovascular outcome when anemia was treated with epoetin-alfa to a target hemoglobin level of 13.5 as compared with 11.3 g/dl. Whether this increase applies to all patient subgroups equally is unclear. We discuss an analysis by Szczech and colleagues of the effects of the higher hemoglobin target in CKD patients with diabetes mellitus or congestive heart failure.
PMID: 20075952
ISSN: 1523-1755
CID: 3534942

More on renal salt wasting without cerebral disease: response to saline infusion [Case Report]

Bitew, Solomon; Imbriano, Louis; Miyawaki, Nobuyuki; Fishbane, Steven; Maesaka, John K
BACKGROUND AND OBJECTIVES/OBJECTIVE:The existence and prevalence of cerebral salt wasting (CSW) or the preferred term, renal salt wasting (RSW), and its differentiation from syndrome of inappropriate antidiuretic hormone (SIADH) have been controversial. This controversy stems from overlapping clinical and laboratory findings and an inability to assess the volume status of these patients. The authors report another case of RSW without clinical cerebral disease and contrast it to SIADH. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:Three patients with hyponatremia, hypouricemia, increased fractional excretion (FE) of urate, urine sodium >20 mmol/L, and concentrated urines were infused with isotonic saline after collection of baseline data. RESULTS:One patient with RSW had pneumonia without cerebral disease and showed increased plasma aldosterone and FEphosphate, and two patients with SIADH had increased blood volume, low plasma renin and aldosterone, and normal FEphosphate. The patient with RSW responded to isotonic saline by excretion of dilute urines, prompt correction of hyponatremia, and normal water loading test after volume repletion. Hypouricemia and increased FEurate persisted after correction of hyponatremia. Two patients with SIADH failed to dilute their urines and remained hyponatremic during 48 and 110 h of saline infusion. CONCLUSIONS:The authors demonstrate appropriate stimulation of ADH in RSW. Differences in plasma renin and aldosterone levels and FEphosphate can differentiate RSW from SIADH, as will persistent hypouricemia and increased FEurate after correction of hyponatremia in RSW. FEphosphate was the only contrasting variable at baseline. The authors suggest an approach to treat the hyponatremic patient meeting criteria for SIADH and RSW and changing CSW to the more appropriate term, RSW
PMID: 19201917
ISSN: 1555-905x
CID: 3464592

Renal salt wasting without cerebral disease: diagnostic value of urate determinations in hyponatremia [Case Report]

Maesaka, J K; Miyawaki, N; Palaia, T; Fishbane, S; Durham, J H C
PMID: 17311074
ISSN: 0085-2538
CID: 3464682

Risk for acute renal failure in patients hospitalized for decompensated congestive heart failure

Chittineni, Harini; Miyawaki, Nobuyuki; Gulipelli, Sailaja; Fishbane, Steven
INTRODUCTION/BACKGROUND:Congestive heart failure (CHF) is an important cause of hospital admissions and is associated with an increased risk for development of acute renal failure (ARF). The purpose of this study was to describe the incidence of ARF, to ascertain risk factors for its development, and to determine whether ARF impacts hospital outcomes. METHODS:Review was conducted of 509 hospital medical records of patients hospitalized with a principal diagnosis of CHF during 2004. ARF was defined as an increase in serum creatinine of 0.5 mg/dl compared to the admission value. Multivariable analysis was used to identify independent predictors of ARF. RESULTS:Most patients had reduced renal function at the time of admission with mean serum creatinine of 1.45 +/- 0.72 and calculated creatinine clearance of 43.1 ml/min. ARF developed during the hospitalization in 21% of patients, with a peak increase in serum creatinine of 0.5-3.3 mg/dl. Most cases occurred on hospital days 4-6 (69.5% of cases). ARF was associated with increased risk for in-hospital mortality and increased length of hospital stay. Risk factors for ARF included diabetes, elevated admission serum creatinine and reduced serum sodium and echocardiographic demonstration of diastolic dysfunction. Neither diuretic nor ACEI/ARB treatment was associated with increased risk. CONCLUSION/CONCLUSIONS:ARF is a common complication among patients hospitalized for CHF, and is associated with increased risk for adverse outcomes. Certain clinical characteristics present at the time of admission help identify patients at increased risk.
PMID: 17259694
ISSN: 1421-9670
CID: 3534932

A patient with an uncommon etiology of intradialytic hypotension [Case Report]

Masani, Naveed N; Miyawaki, Nobuyuki; Maesaka, John K
Hemodialysis is associated with various complications, the most common being intradialytic hypotension (IDH). In the majority of cases, IDH is easily corrected and does not represent a life-threatening condition. We present a patient in whom IDH was unresponsive to various corrective strategies. A new mitral valve regurgitant lesion was diagnosed that eventually led to the patient's demise. Unusual etiologies of IDH need to be considered, particularly in instances where routine therapeutic measures are ineffective.
PMID: 16191186
ISSN: 0894-0959
CID: 3464672

Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency

Behr, Rüdiger; Brestelli, John; Fulmer, James T; Miyawaki, Nobuyuki; Kleyman, Thomas R; Kaestner, Klaus H
Foxa1 is a member of the winged helix family of transcription factors and is expressed in the collecting ducts of the kidney. We investigated its potential contribution to renal physiology in Foxa1-deficient mice on a defined genetic background. Foxa1(-/-) mice are dehydrated and exhibit electrolyte imbalance as evidenced by elevated hematocrit and plasma urea levels, hypernatremia, and hyperkalemia. This phenotype is the consequence of decreased urine osmolality secondary to renal vasopressin resistance. Mutations of the human genes encoding the vasopressin 2 receptor and aquaporin 2 cause nephrogenic diabetes insipidus; however, expression of these genes is maintained or increased, respectively, in Foxa1(-/-) mice. Likewise, expression of the genes encoding the Na-K-2Cl cotransporter (NKCC2), the potassium channel ROMK, the chloride channel CLCNKB, barttin (BSND), and the calcium-sensing receptor (CASR), each of which is important in sodium reabsorption in the loop of Henle, is maintained or even increased in Foxa1-deficient mice. Thus, we have shown that Foxa1(-/-) mice represent a new model of nephrogenic diabetes insipidus with unique molecular etiology, and we have identified the first transcription factor whose mutation leads to a defect in renal water homeostasis in vivo.
PMID: 15252040
ISSN: 0021-9258
CID: 3534912

Hepatic iron in hemodialysis patients [Letter]

Fishbane, Steven; Miyawaki, Nobuyuki; Masani, Naveed
PMID: 15458478
ISSN: 0085-2538
CID: 3534922