Naveed N. Masani

Hyponatremia in Community-Acquired Pneumonia

Background/Aim: Community-acquired pneumonia (CAP) is a frequent cause for hospitalization and may result in a number of different renal and electrolyte complications. The purpose of this study was to describe the incidence of hyponatremia in CAP and to analyze risk factors for its occurrence. Methods: Records were reviewed for all 342 subjects who participated in the Community-Acquired Pneumonia Standardized Order Set study, a 2-year trial of supplemental treatment tools in hospital pneumonia treatment. Results: Hyponatremia (serum sodium concentration <136 mg/dl) was present at hospital admission in 27.9% of patients. The magnitude was generally mild, only 4.1% of patients had serum sodium <130 mEq/l. Patients with hyponatremia had greater initial heart rate (100.2 vs. 93.2 beats/min, p = 0.03), white blood cell count (15,100 vs. 12,100/µl, p < 0.0001) and pneumonia severity index class 4 or 5 (35.7 vs. 25.1% of patients, p = 0.05). Hyponatremia at admission was associated with greater risk for death and increased length of hospital stay. Hyponatremia developed during the hospitalization in 10.5% of subjects, with most cases being mild, only 2.6% of all patients having serum sodium decrease to <130 mEq/l. Patients developing hyponatremia were more likely to have end-stage renal disease and to have had initial intravenous fluids other than isotonic saline, but had similar severity of illness on admission to those without acquired hyponatremia. Conclusion: Hyponatremia is a common complication present at the time of admission for CAP. It is associated with more severe illness, increased mortality risk and extended hospital stays. Hyponatremia develops less frequently during the hospitalization and is unrelated to severity of illness on admission, but is an iatrogenic complication and thus initial treatment with isotonic saline may reduce the risk of this complication.

Membranous Glomerulonephritis with ANCA-Associated Necrotizing and Crescentic Glomerulonephritis

BACKGROUND AND OBJECTIVES Only rare cases of concurrent membranous glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis (NCGN) have been reported. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The authors report the clinical and pathologic findings in 14 patients with MGN and ANCA-associated NCGN. RESULTS The cohort consisted of eight men and six women with a mean age of 58.7 yr. ANCA positivity was documented by indirect immunofluorescence or ELISA in all patients. Indirect immunofluorescence was positive in 13 patients (seven P-ANCA, five C-ANCA, one atypical ANCA). ELISA was positive in nine of 10 patients (five MPO-ANCA, three PR3-ANCA, one MPO- and PR3-ANCA). Clinical presentation included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and acute renal failure (mean creatinine 4.4 mg/dl). Pathologic evaluation revealed MGN and NCGN, with crescents involving a mean of 32% of glomeruli. On ultrastructural evaluation, the majority of cases showed stage I or II membranous changes. Follow-up was available for 13 patients, 12 of whom were treated with steroids and cyclophosphamide. At a mean follow-up of 24.3 mo, five patients progressed to ESRD, seven had stabilization or improvement in renal function, and one had worsening renal function. Five patients, including three with ESRD, died during the follow-up period. The only independent predictor of progression to ESRD was serum creatinine at biopsy. CONCLUSIONS MGN with ANCA-associated NCGN is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute renal failure, and active urine sediment. Prognosis is variable, with 50% of patients reaching endpoints of ESRD or death.

Update on Membranoproliferative GN

Membranoproliferative GN represents a pattern of injury seen on light microscopy. Historically, findings on electron microscopy have been used to further subclassify this pathologic entity. Recent advances in understanding of the underlying pathobiology have led to a proposed classification scheme based on immunofluorescence findings. Dysregulation of the complement system has been shown to be a major risk factor for the development of a membranoproliferative GN pattern of injury on kidney biopsy. Evaluation and treatment of this complex disorder rest on defining the underlying mechanisms.

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.

Acute Tubular Necrosis in a Patient With Myeloma Treated With Carfilzomib

Carfilzomib is a selective proteasome inhibitor approved in 2012 for the treatment of relapsed and refractory multiple myeloma. It was developed with the aim of achieving improved safety profile and greater efficacy in patients who failed conventional treatments. A phase II trial for single-agent carfilzomib analyzed safety data in 526 treated patients and reported a rise in serum creatinine in 127 (24.1%) patients.1 In 73.2% of these 127 patients, the rise in serum creatinine was attributed to the carfilzomib with no other precipitating event identified.1 These data suggest that carfilzomib may be a cause of acute kidney injury (AKI), although the mechanism has not been determined. There have been several case reports providing evidence of AKI secondary to carfilzomib.2, 3, 4, 5, 6, 7 Two recent reports describe thrombotic microangiopathy associated with carfilzomib administration, although causality was not definitively established.4, 5 To our knowledge this is the first case report of biopsy-proven acute tubular necrosis (ATN) in a patient with multiple myeloma who was treated with carfilzomib.

Should Target Hemoglobin Levels in Dialysis Patients be Lowered to 9–10 g/dl?

We have been asked to consider whether the hemoglobin (Hgb) target during ESA treatment for hemodialysis patients should be lowered to 9–10 g/ dl. We will consider this question as a debate proposition and will work through key logical considerations. While there is no broad consensus on a Hgb target range, the proposed range is certainly lower than typical practice. When erythropoietin analogs (the current preferred term is erythropoiesis-stimulating agents [ESA]) were first FDA approved in 1989, clinicians generally sought to raise Hgb levels of hemodialysis patients to approximately 9–10 g/dl. By 1994, the mean Hgb level of patients had increased to above 10 g/dl, in 1999 to above 11 g/dl, and in 2005 to a peak of 12 g/dl (1). At that time, the Kidney Disease Outcomes Quality Initiative (KDOQI) anemia guideline recommended a Hgb target of 11–12 g/dl while FDA product labeling had a Hgb target of 10–12 g/dl. It might, therefore, be surprising that the mean Hgb in 2005 in hemodialysis patients was at the upper end of recommended target ranges. But a general belief in the benefits of therapy and misaligned economic incentives led to an aggressive treatment approach.

Cerebral–Renal Salt Wasting

Cerebral or the preferred term, renal salt wasting (RSW), remains an unresolved syndrome that has historically evolved from being considered nonexistent to acceptance as a distinct clinical syndrome. Yet, differences over its prevalence continue. Many with RSW are diagnosed and treated for SIADH, which has diametrically opposite therapeutic goals from RSW, that is, to water-restrict in SIADH and administer salt and water in RSW. The major obstacles to differentiating SIADH from RSW are the overlapping of significant findings and clinical associations of both syndromes and our inability to assess the volume status of these patients, being volume-depleted in RSW and expanded in SIADH. In this chapter, we (1) redefine RSW, (2) review the pathophysiology of RSW, (3) review relevant volume studies, which prove RSW to be much more common than SIADH in neurosurgical patients, (4) review the complexities of differentiating RSW from SIADH, focusing on how a previously increased FEurate normalizes in SIADH as compared to being persistently increased in RSW after correction of hyponatremia, (5) review the emerging importance of determining fractional excretion (FE) of urate, which surpasses serum urate in the evaluation of hyponatremic conditions, (6) increased FEurate in the presence of normonatremia is suggestive of RSW, (7, 8) A normal FEurate in nonedematous hyponatremia is highly suggestive of reset osmostat, (9) present an algorithm that uses FEurate as central to the evaluation of the hyponatremic patient, (10). demonstrate the presence of a natriuretic factor in RSW that has different characteristics from A/BNP (11) advocate changing cerebral salt wasting to RSW based on reports of RSW occurring in patients without clinical cerebral disease and eliminating reset osmostat as a subtype of SIADH based on a normal FEurate and the predictability of ADH response to changes in serum osmolality, and (12) awareness, that symptoms with potentially serious complications are associated with hyponatremia, creates a therapeutic urgency to improve methods of differentiating RSW from SIADH.

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