Nobuyuki Miyawaki

Risk for Acute Renal Failure in Patients Hospitalized for Decompensated Congestive Heart Failure

Introduction: 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: 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.

More on Renal Salt Wasting Without Cerebral Disease: Response to Saline Infusion

BACKGROUND AND OBJECTIVES 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 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

Cholesterol Metabolism in CKD

Patients with chronic kidney disease (CKD) have a substantial risk of developing coronary artery disease. Traditional cardiovascular disease (CVD) risk factors such as hypertension and hyperlipidemia do not adequately explain the high prevalence of CVD in CKD. Both CVD and CKD are inflammatory states and inflammation adversely affects lipid balance. Dyslipidemia in CKD is characterized by elevated triglyceride levels and high-density lipoprotein levels that are both decreased and dysfunctional. This dysfunctional high-density lipoprotein becomes proinflammatory and loses its atheroprotective ability to promote cholesterol efflux from cells, including lipid-overloaded macrophages in the arterial wall. Elevated triglyceride levels result primarily from defective clearance. The weak association between low-density lipoprotein cholesterol level and coronary risk in CKD has led to controversy over the usefulness of statin therapy. This review examines disrupted cholesterol transport in CKD, presenting both clinical and preclinical evidence of the effect of the uremic environment on vascular lipid accumulation. Preventative and treatment strategies are explored.

Normal fractional urate excretion identifies hyponatremic patients with reset osmostat

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.

Complexity of differentiating cerebral/renal salt wasting from SIADH: Emerging importance of determining fractional urate excretion

The current approach to the diagnosis and treatment of hyponatremia is in a state of flux, largely because of an unresolved controversy regarding the relative prevalence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and cerebral salt wasting, or preferably renal salt wasting (RSW). The recent awareness that symptoms are now being attributed to even mild hyponatremia has led to recommendations to treat virtually all hyponatremics. (Arief et al, 1976; Berl et al, 2010; Decaux, 2006, 2009; Gankam Kegne et al, 2008; Hoorn et al, 2009; Renneboog et al, 2006; Sterns et al,2009; Schrier, 2010) This tendency to treat even mild hyponatremia introduces an urgency to resolve the diagnostic dilemma of differentiating two syndromes, SIADH and RSW, with divergent therapeutic goals, to water-restrict in SIADH or administer salt and water in RSW. We propose to define RSW by supporting data and review the pathophysiology of RSW, the derivation and evolution of the controversy over the relative prevalence of SIADH and RSW, and methods to differentiate SIADH from RSW. We will also review the emerging value of determining fractional excretion (FE) of urate in the evaluation of patients with hyponatremia by emphasizing our recent observations in reset osmostat, identify conditions that predispose to RSW, amplify the possibility that RSW might exist in patients with an increased FEurate without hyponatremia and propose an algorithm where FEurate is central to the evaluation of hyponatremia. We will also advocate and hopefully justify changing the designation, cerebral salt wasting, to renal salt wasting, and briefly discuss different strategies to treat hyponatremia.

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

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.

A patient with an uncommon etiology of intradialytic hypotension.

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 patients demise. Unusual etiologies of IDH need to be considered, particularly in instances where routine therapeutic measures are ineffective.

Fellows’ Forum in Dialysis edited by Mark A. Perazella: A Patient With an Uncommon Etiology of Intradialytic Hypotension

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 patients demise. Unusual etiologies of IDH need to be considered, particularly in instances where routine therapeutic measures are ineffective.

Application of established pathophysiologic processes brings greater clarity to diagnosis and treatment of hyponatremia

Hyponatremia, serum sodium < 135 mEq/L, is the most common electrolyte abnormality and is in a state of flux. Hyponatremic patients are symptomatic and should be treated but our inability to consistently determine the causes of hyponatremia has hampered the delivery of appropriate therapy. This is especially applicable to differentiating syndrome of inappropriate antidiuresis (SIAD) from cerebral salt wasting (CSW) or more appropriately, renal salt wasting (RSW), because of divergent therapeutic goals, to water-restrict in SIAD and administer salt and water in RSW. Differentiating SIAD from RSW is extremely difficult because of identical clinical parameters that define both syndromes and the mindset that CSW occurs rarely. It is thus insufficient to make the diagnosis of SIAD simply because it meets the defined characteristics. We review the pathophysiology of SIAD and RSW, the evolution of an algorithm that is based on determinations of fractional excretion of urate and distinctive responses to saline infusions to differentiate SIAD from RSW. This algorithm also simplifies the diagnosis of hyponatremic patients due to Addison’s disease, reset osmostat and prerenal states. It is a common perception that we cannot accurately assess the volume status of a patient by clinical criteria. Our algorithm eliminates the need to determine the volume status with the realization that too many factors affect plasma renin, aldosterone, atrial/brain natriuretic peptide or urine sodium concentration to be useful. Reports and increasing recognition of RSW occurring in patients without evidence of cerebral disease should thus elicit the need to consider RSW in a broader group of patients and to question any diagnosis of SIAD. Based on the accumulation of supporting data, we make the clinically important proposal to change CSW to RSW, to eliminate reset osmostat as type C SIAD and stress the need for a new definition of SIAD.

Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality. Prevalence estimates vary based on the instruments used to diagnose CKD-aP, and standardized diagnostic instruments are sorely needed. Treatment studies have often yielded conflicting results. This is likely related to studies that are limited by small sample size, flawed designs, and nonstandardized diagnostic instruments. Several large well-designed treatment trials have recently been completed and may soon influence CKD-aP management.