Arnold S. Berns

Urinary Diagnostic Indices in Acute Renal Failure: A Prospective Study

A prospective analysis of the value of urinary diagnostic indices in ascertaining the cause of acute renal failure was undertaken. Our results show that in the setting of acute oliguria a diagnosis of potentially reversible prerenal azotemia is likely with urine osmolality greater than 500 mosm/kg H2O, urine sodium concentration less than 20 meq/litre, urine/plasma urea nitrogen ratio greater than 8, and urine/plasma creatinine ratio greater than 40. Conversely, a urine osmolality less than 350 mosm/kg, urine sodium concentration greater than 40 meq/liter, urine/plasma urea nitrogen ratio less than 3, and urine/plasma creatinine ratio less than 20 suggest acute tubular necrosis. A significant number of oliguric patients will not have urinary indices that fall within these guidelines. In this setting, urine sodium concentration divided by the urine-to-plasma creatinine ratio (the renal failure index) and the fractional excretion of filtered sodium provide a reliable means of differentiating reversible prerenal azotemia from acute tubular necrosis.

The Role of Renal Nerves and Prostaglandins in Control of Renal Hemodynamics and Plasma Renin Activity during Hypotensive Hemorrhage in the Dog

The effects of hypotensive hemorrhage (HH) on renal hemodynamics and plasma renin activity (PRA) during prostaglandin (PG) synthesis inhibition were examined in three groups of dogs. In each group of animals arterial blood pressure was lowered by a 30% decrement. In the first group of eight control animals, HH was not associated with a significant change in glomerular filtration rate (GFR, 42-36 ml/min, NS); renal blood flow (RBF) declined significantly, from 234 to 171 ml/min, P < 0.05. In the second group of eight animals, pretreated with RO 20-5720 (RO, 2 mg/kg), a competitive inhibitor of PG synthesis, HH was associated with a significant fall in GFR (43-17 ml/min, P < 0.001) and RBF (195-89 ml/min, P < 0.001). In the third group of eight animals, pretreatment with indomethacin (IN, 10 mg/kg), a chemically dissimilar PG inhibitor, HH was also associated with a significant fall in GFR (38-8 ml/min, P < 0.001) and RBF (150-30 ml/min, P < 0.001). Renal denervation attenuated this renal ischemic effect of HH in the presence of PG inhibition. In the RO group, GFR (34 vs. 17 ml/min, P < 0.005) and RBF (145 vs. 89 ml/min, P < 0.025) were significantly greater in denervated vs. innervated kidneys during HH. Similarly, in animals treated with IN, a significantly higher GFR (28 vs. 8 ml/min, P < 0.005) and RBF (101 vs. 30 ml/min, P < 0.005) occurred in denervated as compared to innervated kidneys during HH. With HH, the increase in PRA in the control group (3.34-11.68 ng/ml per h, P < 0.005) was no different than that observed in the RO group (4.96-18.9 ng/ml per h, P < 0.001) or IN group (4.71-17.8 ng/ml per h, P < 0.001). In summary, the present results indicate that renal PG significantly attenuate the effect of HH to decrease GFR and RBF. Furthermore, renal denervation exerts a protective effect against the enhanced renal ischemic effects which occur in the presence of PG inhibition during HH. Finally, PG inhibition does not alter the effect of HH to cause an increase in PRA.

Mechanism of Effect of Hypoxia on Renal Water Excretion

The effect of lowering the pressure of oxygen from 80 to 34 mm Hg was examined in anesthetized dogs that were undergoing a water diuresis. This degree of hypoxia was associated with an antidiuresis as urine osmolality (Uosm) increased from 107 to 316 mosmol/kg H(2)O (P < 0.001) and plasma arginine vasopressin increased from 0.06 to 7.5 muU/ml, (P < 0.05). However, hypoxia was not associated with significant changes in cardiac output (CO, from 4.2 to 4.7 liters/ min), mean arterial pressure (MAP, from 143 to 149 mm Hg), glomerular filtration rate (GFR, from 46 to 42 ml/min), solute excretion rate (SV, from 302 to 297 mosmol/min), or filtration fraction (from 0.26 to 0.27, NS). Hypoxia was associated with an increase in renal vascular resistance (from 0.49 to 0.58 mm Hg/ml per min, P < 0.01). The magnitude of hypoxia-induced antidiuresis was the same in innervated kidneys and denervated kidneys. To further examine the role of vasopressin in this antidiuresis, hypoxia was induced in hypophysectomized animals. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in hypophysectomized animals was the same as in intact animals. In contrast to intact animals, however, hypoxia did not induce a significant antidiuresis in hypophysectomized animals (Uosm from 72 to 82 mosmol/kg H(2)O). To delineate the afferent pathway for hypoxia-stimulated vasopressin release, hypoxia was induced in dogs with either chemo- or baroreceptor denervation. The effect of hypoxia on CO, MAP, GFR, SV, and renal blood flow in the denervated animals was the same as in nondenervated animals. Hypoxia resulted in an antidiuresis in chemoreceptor (Uosm from 113 to 357 mosmol/kg H(2)O, P < 0.001) but not in baroreceptor (Uosm from 116 to 138 mosmol/kg H(2)O, NS) denervated animals. To determine if hypoxia alters renal response to vasopressin, exogenous vasopressin was administered to normoxic and hypoxic groups of dogs. The antidiuretic effect of vasopressin was no different in these two groups. These results demonstrate that hypoxia induces an antidiuresis which is independent of alterations in CO, MAP, SV, filtration fraction, renal nerves, or renal response to vasopressin and occurs through baroreceptor-mediated vasopressin release. The nature of the baroreceptor stimulation remains to be elucidated.

1,25 dihydroxycholecalciferol effects in chronic dialysis. A double-blind controlled study.

1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.

Cost, Quality, and Value: The Changing Political Economy of Dialysis Care

“One of the essential qualities of the clinician is interest in humanity, for the secret of the care of the patient is caring for the patient.” —Frances Weld Peabody, MD (1881 to 1927)[1][1] Clinical nephrology, perhaps more than any other medical subspecialty, has been shaped by a single

Lactic Acidosis from Carboxyhemoglobinemia After Smoke Inhalation

Tissue hypoxia as a result of a wide variety of clinical situations had frequently been implicated as a cause of systemic acidosis due to the accumulation of lactic acid. Four patients suffering from smoke inhalation had lactic acidosis in association with carboxyhemoglobinemia. There was no evidence of decreased tissue perfusion, hypotension, arterial hypoxemia, or anemia. The following were tested in all patients: arterial pH (7.25 to 7.40), Pco-2 (19 to 27 mm Hg), Po (63 to 116 mm Hg), HCO-2- (11 to 19 meq/litre), carboxyhemoglobin (13% to 37%), and lactic acid (5.1 to 9.3 meq/litre). After therapy with oxygen and intravenous corticosteroids, there was prompt return of lactic acid levels, carboxyhemoglobin values, and arterial pH to normal. It is concluded that the cause of lactic acidosis in the presence of carboxyhemoglobinemia during smoke inhalation is tissue hypoxia. This tissue hypoxia is due to the reduction of the oxygen-carrying capacity of the blood and the concomitant shift of the oxyhemoglobin dissociation curve to the left, both known to result from carboxyhemoglobinemia.

The Patient-Centered Medical Home and Nephrology

The notion of a patient-centered medical home (PCMH) is rapidly gaining traction as the latest idea to transform health care delivery in the United States. In broad terms, PCMH is “a physician-directed practice that provides care that is accessible, continuous, comprehensive and coordinated and

Magnesium-induced bradycardia.

Excerpt Depression of sinoatrial and atrioventricular conduction due to severe hypermagnesemia (serum magnesium concentration, 10 to 15 meq/litre) has been previously well documented (1-3). We rece...

Controlled Trial of the Effects of 1,25-Dihydroxycholecalciferol in Patients Treated with Regular Dialysis

In a double-blind controlled study, 15 patients received 1,25-dihydroxycholecalciferol (1,25[OH]2D3) (0.5-1.5 microgram/day) and 16 patients received vitamin D3 (D3) (400-1,200 IU/day). The patients receiving 1,25(OH)2D3 had a rise in mean serum calcium concentration from 9.05 +/- 0.15 to 10.25 +/- 0.20 mg/dl (p less than .001) with a return to 9.37 +/- 0.16 (p less than .001) in the post-control period; however, hypercalcemia (greater than 11.5 mg/dl) occurred in 5 of 15 patients. Likewise, patients who received 1,25(OH)2D3 but not those given D3 had a reversible decrease in immunoreactive parathyroid levels. 9 of 12 patients given D3 had serial iliac crest bipsies showing histologic deterioration, while 6 of 7 patients who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium content decreased in patients on D3 (p less than .05) but not in those on 1,25(OH)2D3. We conclude that the administration of 1,25(OH)2D3 to dialysis patients: (1) has a calcemic effect. (2) decreases levels of immunoreactive parathyroid hormone, and (3) is associated with histologic improvement in bone disease.

Managing Conflicts of Interest: The Road Ahead

Recent allegations have accused “respected experts” for purportedly promulgating information and opinions to physician-consumers while concealing their conflicts of interest (COIs) and commercial bias.1 The news blitz stemming from these transgressions has led to intense examination of the relationship between physicians and companies that sell medical products and devices. Universities, professional societies, and government agencies uniformly condemn such practice and endorse a variety of methods to reduce the likelihood of commercial influence on activities that are designed to be objective.2,3 In 2008, the American Society of Nephrology (ASN) created a committee to review the Society’s policies and practices regarding its interface with commercial interests. The committee submitted its ensuing report to the ASN Council and published a summary of its final recommendations—which were unanimously approved by council—in this issue of JASN.4 There are four largely separate but contiguous processes whereby commercial interests could influence how physicians provide treatment to patients: conducting research, publishing scientific information, educating practitioners, and developing policy. ASN s educational efforts comprise the majority of the Society’s interactions with commercial interests and, not incidentally, draw the most national attention from the perspective of potential COI and commercial bias. Thus, ASN conducts its major activity squarely in the sights of those who seek to eliminate the possibility of commercial influence in the process of educating practitioners.5 The ASN Committee on Corporate Relations struggled with the meaning and definition of COI. It is widely recognized that everyone has some form of conflict. Although we did not develop a unique definition, we generally agree with the definition proposed by the Institute of Medicine (IOM).6 The practical consequence of this definition is that identifying COI should focus on financial conflicts because they are more objective and better suited to regulatory scrutiny. However, although the committee focused its analysis on financial entanglements, we recognize that professional conflicts should be considered when implementing the proposed recommendations. This emphasis on financial conflicts transforms the focus of bias. We considered one definition of bias as “a conclusion or recommendation based on opinion unsupported by facts.” According to this definition as applied to medicine, almost no recommendation can be totally unbiased. The practical resolution of this matter is to focus on commercial bias, which the committee defines as “an inadequately supported judgment or recommendation about the use of a commercial product.” The committee made no recommendation regarding the highly controversial issue of continuing medical education (CME) funding. However, the sentiment of the committee is more closely aligned with IOM’s recommendations rather than other recommendations directed at eliminating industry support for CME.5,6 The IOM report makes two important points. First, CME is essential to providing high-quality care to patients and, therefore, its importance is increasing. Second, there is no information on the consequences of making a dramatic shift in funding for CME. Making a major change in how CME is funded in the absence of data will have unforeseen consequences.6 The committee generally agrees that any changes should be subject to careful review and testing. The committee strongly endorses the concept that there should be clear separation between the development of the content of educational programs and the generation of financial support. We are impressed with how well ASN has implemented this policy during the past few years. Although virtually everyone can agree that there should be no commercial bias in CME activities, there is surprisingly little understanding of the practical implications of this policy. There are two processes for uncovering potential COI and commercial bias. The first is the process of disclosure. The second is the evaluation of presentations by designated observers and participants. Disclosure is strongly endorsed by all groups. The Accreditation Council for Continuing Medical Education (ACCME) requires disclosure of accredited providers, including ASN. However, what should a speaker disclose? There is wide agreement that a speaker should disclose all financial relationships with commercial entities. In addition, some interPublished online ahead of print. Publication date available at www.jasn.org.