Joseph Mattana

Predictors of Survival in HIV-Infected Patients on Hemodialysis

We undertook the present study to determine whether there might be variables other than CD4 counts which might help predict survival of HIV-infected patients who are placed on chronic hemodialysis, survival which often is extremely poor. We studied prospectively (n = 18) and retrospectively (n = 6) 24 consecutive HIV-positive patients on chronic hemodialysis at our institution over a 7-year period and recorded clinical and laboratory variables at the time of initiation of dialysis. The mean survival for the group as a whole was 11 +/- 8 (range 2-32) months. A highly significant positive correlation was found between survival and CD4 counts (p < 0.001) and blood pressure (systolic, p < 0.02; diastolic, p < 0.05; mean arterial, p < 0.05). Infection rate and urine protein excretion both had significant negative correlations with survival (p < 0.01 and p < 0.02, respectively). The presence of edema appeared to have a positive effect on survival (p < 0.01). The use of antiretroviral therapy resulted in significantly greater survival of HIV-infected patients (15.2 +/- 2.2 vs. 6.2 +/- 1.2 months, p < 0.01). Using a general linear model, it was found that CD4 count and systolic, diastolic, and mean arterial blood pressures and infection rate all were independent estimators of survival. We conclude that variables other than CD4 counts might also be useful in predicting survival in HIV-infected patients on chronic hemodialysis.

Career Choice Selection and Satisfaction among US Adult Nephrology Fellows

Although many anticipate that there will be an eventual shortage of practicing nephrologists, a complete understanding is lacking regarding the current factors that lead US adult nephrology fellows to choose nephrology as a career and their satisfaction with this choice. It is of great concern that interest in obtaining nephrology fellowship training continues to decline in the United States, especially among US medical graduates, and the reasons for this are unclear. The exposure that students and residents have to nephrology is likely to play an important role in the career choices that they make and their ultimate satisfaction with this career choice is likely influenced by several factors, including job opportunities. Some of the findings presented here suggest that there may be a high percentage of nephrology fellows who are dissatisfied with their career choice. Failure to understand the factors that influence trainees to choose nephrology as a career and those that affect their satisfaction with this choice may impair the ability to graduate a sufficient number of nephrologists to meet projected demand. In this article, a number of variables related to the choice of nephrology as a career and satisfaction with a career in nephrology are discussed. Some steps that the nephrology training community might take to help promote interest in nephrology and optimize the satisfaction that nephrology graduates derive from their careers are also proposed.

Morphine stimulates mesangial cell TNF-alpha and nitrite production.

Background: Intravenous opiate abusers are susceptible to develop heroin and HIV-associated nephropathies; however, the role of opiates in the development of these kidney lesions is not clear. Patients with opiate addiction are prone to recurrent infections. Methods: The effect of morphine was studied on the generation of TNF-α with or without LPS (lipopolysaccharide) by cultured mouse mesangial cells. In addition, the effect of morphine was evaluated on mesangial cell nitrite production. To evaluate the role of opiate receptors, we studied the effect of naloxone and naltrexone on mesangial cell TNF-α and nitrite production. To determine the role of TNF-α on mesangial cell nitrite production, we examined the effect of anti-TNF-α antibody on morphine-induced nitrite production. Assay of TNF-α and nitrite production was carried by ELISA and Griess method respectively. Results: Morphine alone did not enhance the generation of TNF-α by mesangial cells, however, an enhanced (P < 0.001) TNF-α production was observed when mesangial cells were first treated with morphine for 18 h and then activated further with LPS. Maximum release of TNF-α was seen at a concentration of 10−12 M of morphine. Opiate receptor antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite production. Anti-TNF-α antibody attenuated morphine induced nitrite generation. Conclusion: We conclude that morphine stimulates the generation of TNF-∝ by LPS-activated mesangial cells. This effect of morphine seems to be opiate receptor mediated and has a downstream effect in the form of mesangial cell nitrite generation. The present in vitro study provides the basis for a hypothesis that morphine may be playing a role in the development of heroin and HIV-associated nephropathies.

Personal Digital Assistants: A Review of Their Application in Graduate Medical Education

Personal digital assistants (PDAs) have become widely used in medicine and may be especially useful in achieving the goals of graduate medical education. The complex challenges that residents and their program directors in graduate medical education programs confront may be met more readily with the use of these devices. The PDA’s ability to serve as an informational database, an organizer of patient-specific information, a tracking tool that can be used by program directors to enhance curriculum design, and a tool for conducting education research are some of the ways that these devices might favorably affect residency training in graduate medical education programs.

Enhancing interest in nephrology careers during medical residency.

Promoting interest in nephrology as a career is vital to sustain a workforce adequate to meet the projected demand for nephrologists. The educational experiences that internal medicine residents have may play an important role in influencing such choices, and attempts to enrich such experiences could prove a useful strategy to help facilitate interest in careers in nephrology. Like many electives, nephrology rotations typically consist of activities heavily weighted toward inpatient care. This type of elective is unlikely to provide a representative exposure to the breadth of nephrologists roles and may lack sufficient mentoring opportunities. We describe an innovative design for a nephrology elective that provides residents with educational experiences in both inpatient and outpatient venues and exposure to faculty with diverse interests and areas of expertise. Our experience with this elective in comparison to a traditional inpatient-based elective suggests that the combined elective format is perceived favorably by medical residents and provides them with a better educational experience, more representative exposure to nephrology, positive mentoring experiences, and the potential for greater interest in pursuing nephrology as a career. Our findings offer the possibility that interventions at the level of medical resident education might be a means to help promote interest in careers in nephrology.

Oxidation of the Mesangial Matrix Metalloproteinase-2 Impairs Gelatinolytic Activity

Glomerulosclerosis is characterized by an accumulation of mesangial extracellular matrix. Oxygen radicals are strongly implicated in glomerular injury but it is unclear by what mechanism they could modulate matrix turnover dynamics. We evaluated whether oxidation of the 72 kD mesangial matrix metalloproteinase-2 (MMP-2), the major mesangial matrix-degrading enzyme, could alter its gelatinolytic activity. Oxidation of the MMP-2 using a FeCl3/ascorbate system resulted in impaired ability to degrade [3H]gelatin compared to control. Samples were also subjected to SDS-PAGE gelatin substrate zymography. At the 72 kD position a significant impairment of gelatinolytic activity of oxidized samples was observed, a decrease attenuated by coincubation of samples with the FeCl3/ascorbate system plus the radical spin trap N-tert-butyl-α-phenylnitrone suggesting specificity of oxidative changes in the decrease in enzymatic activity. These data represent the first report demonstrating that oxidation of the MMP-2 diminishes its activity and suggest a previously undescribed mechanism by which oxygen radicals may contribute to altered turnover of extracellular matrix.

Effects of Prostaglandin E2 on Mesangial Cell Migration

Mesangial cell migration is a feature of certain renal diseases such as mesangiocapillary glomerulonephritis, a disorder which responds to treatment with cyclo-oxygenase inhibitors. We undertook the present study to determine whether prostaglandin E2 (PGE2) might have a direct effect on mesangial cell migration. PGE2 (10(-8) M) treated cells migrated a mean percent area of 16.8 +/- 0.5 during 24 h when compared to control cells which migrated only a mean percent area of 10.3 +/- 0.8 (p < 0.001). At 48 h, PGE2-treated cells migrated a mean percent area of 21.7 +/- 1.1 when compared to control cells which migrated only a mean percent area of 14.7 +/- 1.4 (p < 0.01). Meclofenamate (10(-5) M), a cyclo-oxygenase inhibitor, significantly (p < 0.02) inhibited migration of mesangial cells (at 48 h controls 13.4 +/- 0.5 vs. meclofenamate-treated cells 3.2 +/- 0.8). Since meclofenamate attenuates basal production of PGE2 by mesangial cells, inhibition of migration by mesangial cells by meclofenamate indicates that the basal production of PGE2 by mesangial cells also significantly contributes to the migration of mesangial cells. 3-Isobutyl-1-methylxanthine (IBMX, 10(-3) M), a phosphodiesterase inhibitor, also significantly (p < 0.001) enhanced migration of mesangial cells (controls 13.4 +/- 0.5 vs. IBMX-treated cells 20.8 +/- 0.5). These results suggest that mesangial cell migration is directly enhanced by PGE2. The present study provides a rationale for the use of cyclo-oxygenase therapy in patients with mesangiocapillary glomerulonephritis.

Hemoglobin oxygen saturation discrepancy using various methods in patients with sickle cell vaso‐occlusive painful crisis

Abstract:u2002 Objective:u2002To evaluate agreement among various methods for measuring oxyhemoglobin (O2Hb) saturation in adult hypoxic patients with sickle cell disease (SCD) during painful vaso‐occlusive crisis and to compare those results with a control group. Patients and methods: The hemoglobin oxygen saturation was determined simultaneously by pulse oximetry (SpO2), co‐oximetry [SO2 (functional oxyhemoglobin saturation) and FO2Hb (oxyhemoglobin fraction)] and by calculation (SaO2) using a normal O2Hb dissociation curve in 18 adult patients with SCD during vaso‐occlusive crisis and 12 non‐SCD patients with various cardiopulmonary diagnoses. The method proposed by Bland and Altman was used to evaluate agreement of various methods in each of the two groups. Results: Mean differences between various methods in patients with SCD were significantly larger than the control group. Limits of agreement (LOA) were also wider in the SCD group than in the control group. Mean bias between SpO2 and SO2, and SpO2 and FO2Hb in patients with SCD were −3.1u2003±u20034.4 (LOA: −11.9 to 5.7) and 2u2003±u20034.1 (LOA: −6.2 to 10.2) respectively, compared with −1.4u2003±u20031.4 (LOA: −4.2 to 1.4) and 1.2u2003±u20031.5 (LOA: −1.9 to 4.3) in the control group. A mean bias of −4.5u2003±u20034 (LOA: −12.5 to 3.5) between SpO2 and SaO2 was noted in patients with SCD compared with −0.1u2003±u20032.1 (LOA: −4.3 to 4.1) in the control group. The width of LOA for various methods in patients with SCD ranged from 9.8 to 17.6 compared with 1.3 to 8.4 in the control group. Conclusion: Patients with SCD during vaso‐occlusive crisis have discrepancies in O2Hb saturation measurements by various methods. Abnormal pulse oximetry values in these patients should be interpreted cautiously and supplemented by arterial blood gas analysis and co‐oximetry.

UNDERDIAGNOSIS OF CHRONIC KIDNEY DISEASE IN THE NURSING HOME POPULATION

To the Editor: Chronic kidney disease (CKD) is present in more than 12% of Americans aged 65 and older. In the guidelines from the National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative, age 60 and older is indeed considered to be a major risk factor for CKD. Among various complications, CKD appears to independently predict mortality and cardiovascular disease. 5 Readily available formulas for calculating glomerular filtration rates (GFRs), along with a staging system and CKD stage-dependent therapeutic guidelines, have simplified the ability to identify CKD, categorize its severity, and implement appropriate treatment. Nevertheless, several reports suggest that CKD is underdiagnosed and undertreated. The purpose of this study was to explore how frequently physicians of elderly nursing home residents, who have CKD based on NKF criteria, address this diagnosis. After institutional review board approval was obtained, a retrospective chart review was conducted of all long-term residents in a 672-bed facility aged 60 and older who had resided there for at least 6 months and whose records included at least two serum creatinine levels drawn at least 90 days apart from each other. Each subject’s monthly physician progress notes over the previous 6 months were reviewed to determine whether a diagnosis of CKD was recorded. The Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (C-G) formulas were used to estimate subjects’ GFRs, with values less than 60 mL/min per 1.73 m of body surface area regarded as positive screening tests for CKD. Serum creatinine values recommended for identification of CKD ( 1.5 mg/dL for men, 1.3 mg/dL for women) were also used as screening criteria for CKD. Two hundred eighty patients met the criteria. Of those with CKD according to MDRD and C-G criteria, a diagnosis of CKD was not noted in 62% and 82%, respectively, of the charts. Of women with CKD according to MDRD and C-G criteria, 70.4% and 87%, respectively, had no notation of CKD in their charts. A diagnosis of CKD was omitted less often in men with CKD (35.3% and 62.9% when identified according to MDRD and C-G, respectively). A diagnosis of CKD was also frequently omitted from charts of patients with CKD based on aforementioned sex-based serum creatinine values as well. Using logistic regression analysis (P 5.02), when controlling for age, sex was found to significantly affect the likelihood of CKD being recognized. Men had only 0.25 odds of underdiagnosis of CKD when compared with women (P 5.049). When sex was controlled for, there was no significant relationship between age groups and underdiagnosis using the MDRD equation (Table 1). Using patients with CKD according to C-G, a similar effect of sex was observed using logistic regression (P 5.01), but when sex was controlled for, patients who were aged 71 to 80 had only a 0.23 odds of underdiagnosis when compared with those aged 90 and older (P 5.02). Delayed recognition and therapy of CKD may predispose patients to adverse outcomes, and these data suggest that CKD may be substantially underdiagnosed in the elderly nursing home population. Although CKD was addressed in only a minority of patients in whom it was evident using GFR estimations, the presence of CKD was documented more frequently when using the creatinine-based parameters described previously. Although there are a number of potential explanations why such a difference was observed, it may simply be that an overtly high serum creatinine level will be more likely to draw the physician’s attention than a relatively ‘‘normal’’ appearing serum creatinine level that nevertheless corresponds with a diminished GFR that has not been calculated. The NKF guidelines not only recommend use of GFR estimation equations, but also expressly declare use of serum creatinine alone not to be optimal in assessment of kidney function. Although GFR calculations and serum creatinine have limitations, these data nevertheless suggest substantial underdiagnosis of CKD, even with serum creatinine levels above 1.4 mg/dL. In summary, despite well-established criteria for the diagnosis of CKD, including simple methods to estimate GFR, CKD appears to be underdetected within the nursing home setting, potentially placing this community at risk for costly, avoidable outcomes. This study underlines the effect of age and sex on misdiagnosis of CKD. Further studies will

Relationship between dialysate oxidized protein and peritoneal membrane transport properties in patients on peritoneal dialysis

BACKGROUNDnIncreased levels of oxidized proteins have been reported in the serum of patients with end-stage renal disease, though little is known regarding the oxidized protein content of the dialysate in patients on peritoneal dialysis (PD) and no information is available as to how this may correlate with important clinical and laboratory variables, including abnormal peritoneal membrane function. In this study we attempted to identify oxidized proteins in the dialysate of patients on PD using western blot analysis, and examined the relationship between these proteins and the function of the peritoneal membrane and other clinical and laboratory variables.nnnMETHODSnPeritoneal dialysate and serum samples were obtained from 18 patients on PD, and western blot analysis using an antibody to oxidized protein was carried out with reprobing for albumin. Oxidized protein/albumin ratios were determined and compared with various clinical and laboratory variables including peritoneal equilibration test results.nnnRESULTSnOxidized protein/albumin ratios were higher in the dialysate of patients who were high/high average transporters compared to low/low average transporters. Oxidized protein ratios were also found to be higher in the dialysate of patients who had diminished urine output as a reflection of loss of residual renal function. Negative correlations were noted between oxidized protein ratios in the dialysate and serum albumin levels and creatinine clearance.nnnCONCLUSIONSnHigher levels of oxidized protein in the dialysate appear to be correlated with high/high average peritoneal membrane transport characteristics and may be related to loss of residual renal function. These preliminary findings suggest that it is plausible that oxidized proteins in the dialysate might play a contributory role in complications including membrane damage and ultrafiltration failure in patients on PD.