Benjamin J. Freda

Cardiac troponins in renal insufficiency: review and clinical implications.

Patients with renal insufficiency may have increased serum troponins even in the absence of clinically suspected acute myocardial ischemia. While cardiovascular disease is the most common cause of death in patients with renal failure, we are just beginning to understand the clinical meaning of serum troponin elevations. Serum troponin T is increased more frequently than troponin I in patients with renal failure, leading clinicians to question its specificity for the diagnosis of myocardial infarction. Many large-scale trials demonstrating the utility of serum troponins in predicting adverse events and in guiding therapy and intervention in acute coronary syndromes have excluded patients with renal failure. Despite persistent uncertainty about the mechanism of elevated serum troponins in patients with reduced renal function, data from smaller groups of renal failure patients have suggested that troponin elevations are associated with added risk, including an increase in mortality. It is possible that increases in serum troponin from baseline in patients with renal insufficiency admitted to hospital with acute coronary syndrome may signify myocardial necrosis. Further studies are needed to clarify this hypothesis.

Distribution of Peyer's patches in the distal ileum

Background and AimsPeyers patches play a major role in intestinal immunity, are portals of entry for significant pathogens, and may be important in Crohns disease. Whereas their microscopic anatomy and immune function are well described, surprisingly little is known of their macroscopic anatomy and distribution. Our aim was to assess their number, area, and distribution in the normal distal ileum, with particular reference to patient age. MethodsDistal ilea (200 cm) obtained at autopsy from 55 adults without intestinal disease were opened along the mesenteric border, fixed in acetic acid, and transilluminated. Peyers patches were counted, and the length, breadth, and distance from the ileocecal valve were recorded. ResultsPatches were most numerous in the terminal 10–15 cm where they formed a lymphoid ring. More proximal patches were oval, antimesenteric, and irregularly spaced. By area, 46% of patch tissue occurred in the terminal 25 cm. The mean number of patches ranged from 29.4 ± 5.4 in the youngest group studied, to 19.0 ± 3.0 in the oldest. Total patch area was greatest in the group aged 21–30 (47.4 ± 1.0 cm2). ConclusionPeyers patches are concentrated in the distal 25 cm of ileum but extend proximally for 200 cm. The variation in their size, shape, and distribution in different individuals is greater than often appreciated and may influence the presentation of diseases centered on these structures.

Management of hyponatremia: Providing treatment and avoiding harm

Hyponatremia, in its most severe form, requires urgent infusion of hypertonic saline to correct cerebral edema. However, overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome. The authors review the treatment of hyponatremia in order to provide clinicians with a sound approach in a variety of settings in which severity, symptoms, and underlying disease states influence therapy. Also discussed is the current role of vasopressin antagonists in treatment. Undercorrection of acute symptomatic hyponatremia can lead to serious neurologic injury, but so can overly rapid correction of chronic hyponatremia.

The role of Peyer's patches in the age-related incidence of Crohn's disease

Recently researchers have suggested that clinical subsets of Crohns disease occur, which are variously described as inflammatory, fibrostenotic, and fistulizing. In addition, it has been observed that within families with multiple cases, often there is concordance of the site and type of disease. The lesions of Crohns disease occur in segments that suggest that distribution of Peyers patches. When the age-related incidence of Crohns disease was plotted for all countries from which such data were available, the peaks of greatest case frequency occurred at ages 15 to 25 years and paralleled a similar peak representing the number of Peyers patches as a function of age. This correlation suggests that Crohns disease may develop as an inflammatory process specifically targeting these important lymphoid structures. Similar peaks of activity in the adolescent to early adult years occur for appendicitis and tonsillitis.

A clustering of Crohn's disease in Mankato, Minnesota

Infrequently, clusterings of Crohns disease (CD) occur that suggest it is transmissible. We studied such a clustering. Graduates of the Mankato West High School Class of 1980 were contacted by mail and asked to respond, by self-addressed postcard, to a six-item questionnaire about inflammatory bowel disease and CD. Responses were followed-up by telephone contact and additional mailings. Two visits were made to Mankato, Minnesota, to interview individuals with CD, to obtain medical records, radiographs, and sera, and to study environmental risk factors. Of the 320 graduates of the class of 1980, 285 were contacted. Seven cases of CD were identified, the equivalent of a prevalence of 2,400/100,000. Concerns were discovered that CD may have emanated from recreational swimming. Fecal coliform counts in excess of 200/dL, the standard above which water is regarded as unsafe for recreational use, had been recorded year after year for the Blue Earth River at Mankato and for the Minnesota River. Recent fecal coliform counts (1993–1995) of Lake Washington, Lake German/Jefferson, and Lake Shetek were greater than 200/dL in 57%, 65%, and 62% of water samples. This clustering, in unrelated individuals, argues against a genetic cause for CD and suggests that environmental transmission occurred.

Cardiovascular responses to muscle contraction following microdialysis of nitric oxide precursor into ventrolateral medulla

We determined the effects of administering L-arginine, a precursor for the synthesis of nitric oxide, and L-NMMA (NG-monomethyl-L-arginine), a nitric oxide synthase blocker, into the rostral (RVLM) and caudal (CVLM) ventrolateral medulla on cardiovascular responses elicited during static contraction of the triceps surae muscle. Two microdialysis probes were inserted bilaterally into the RVLM or CVLM of anesthetized Sprague-Dawley rats using stereotaxic guides. For RVLM experiments, static muscle contraction evoked by stimulation of the tibial nerve increased mean arterial pressure (MAP) and heart rate (HR) by 29+/-3 mmHg and 44+/-7 bpm, respectively (n=8). Microdialysis of L-arginine (1.0 microM) for 30 min attenuated the contraction-evoked increases in MAP and HR. After discontinuing L-arginine, L-NMMA (1.0 microM) was microdialyzed into the RVLM for an additional 30 min followed by a muscle contraction. This contraction augmented the pressor response (37+/-4 mmHg) and HR (61+/-11 bpm) with respect to control values. For CVLM experiments, muscle contraction increased MAP and HR by 23+/-3 mmHg and 25+/-5 bpm, respectively (n=9). Microdialysis of L-arginine (1.0 microM) for 30 min potentiated the contraction-evoked increases in MAP and HR. Subsequent administration of L-NMMA (1.0 microM) into the CVLM for an additional 30 min blocked the augmented MAP and HR responses. Developed tensions did not alter during contractions throughout both RVLM and CVLM protocols. These results suggest that nitric oxide, within the RVLM and CVLM, plays an opposing role in modulating cardiovascular responses during static muscle contraction.

Decongestive Treatment of Acute Decompensated Heart Failure: Cardiorenal Implications of Ultrafiltration and Diuretics

In patients with acute decompensated heart failure (ADHF), treatment aimed at adequate decongestion of the volume overloaded state is essential. Despite diuretic therapy, many patients remain volume overloaded and symptomatic. In addition, adverse effects related to diuretic treatment are common, including worsening kidney function and electrolyte disturbances. The development of decreased kidney function during treatment affects the response to diuretic therapy and is associated with important clinical outcomes, including mortality. The occurrence of diuretic resistance and the morbidity and mortality associated with diuretic therapy has stimulated interest to develop effective and safe treatment strategies that maximize decongestion and minimize decreased kidney function. During the last few decades, extracorporeal ultrafiltration has been used to remove fluid from diuretic-refractory hypervolemic patients. Recent clinical studies using user-friendly machines have suggested that ultrafiltration may be highly effective for decongesting patients with ADHF. Many questions remain regarding the comparative impact of diuretics and ultrafiltration on important clinical outcomes and adverse effects, including decreased kidney function. This article serves as a summary of key clinical studies addressing these points. The overall goal is to assist practicing clinicians who are contemplating the use of ultrafiltration for a patient with ADHF.

Renal Sarcoidosis Presenting as Acute Kidney Injury With Granulomatous Interstitial Nephritis and Vasculitis

Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis.

How Benign Is IgA Nephropathy with Minimal Proteinuria

nosis and treatment. 2,3 The natural history of IgAN can range from clinically silent urinary abnormalities and preserved renal function over many decades to ESRD. Progression to ESRD occurs in 10%–50% of patients, usually developing slowly over 20 years. 4,5 Ten-year renal survival rates (62%–98%) are also highly variable. 6,7 In regions where renal biopsies are routinely performed for isolated urinary abnormalities (microscopic hematuria, minimal proteinuria ,0.5 g/d), the incidence of IgAN is higher, and the estimates of renal survival are affected by lead-time bias. A more fully informed understanding of the natural history of IgAN across its entire clinical and histologic spectrum could assist clinicians in assessing prognosis and implementing treatment. Muchhasbeenlearnedoverthelast20–30yearsregarding risk stratification of IgAN. 3 Clinical parameters that correlate with increased risk of progression of disease include proteinuria .1 g/d, hypertension, and reduced GFR. The impact of these variables on prognosis is strengthened when they are followed over time. In contrast to other glomerular diseases, proteinuria in IgAN at an excretion rate of even 0.5–1.0 g/d is associated with risk of ESRD. 3

What Is the Optimal Treatment for Patients With Atherosclerotic Renal Artery Stenosis

Address correspondence to Barbara Greco, MD, 100 Wason Ave, Suite 200, Springfield, MA 01107. E-mail: barbara.greco@ baystatehealth.org 2014 by the National Kidney Foundation, Inc. 0272-6386/