Robert M. Perkins

Effect of Pentoxifylline on GFR Decline in CKD: A Pilot, Double-Blind, Randomized, Placebo-Controlled Trial

BACKGROUND Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression. STUDY DESIGN Pilot randomized double-blind placebo-controlled trial. SETTING & PARTICIPANTS 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility. INTERVENTION Pentoxifylline, 400 mg twice daily, or matching placebo. OUTCOMES Difference in rates of estimated GFR change during the 1-year study period between the 2 groups. MEASUREMENTS Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment. RESULTS Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year. LIMITATIONS Small sample size and incomplete follow-up. CONCLUSIONS Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.

Hyperkalemia After Packed Red Blood Cell Transfusion in Trauma Patients

BACKGROUND Published analyses of clinical outcomes for patients requiring large-volume blood transfusion conflict with respect to the impact upon plasma potassium levels. We analyzed a cohort of trauma patients to ascertain the impact of component product transfusion upon plasma potassium values. METHODS We performed an observational analysis of previously, prospectively collected clinical data on 131 noncrush trauma patients undergoing resuscitation during the initial 12 hours after admission to a combat support hospital. Comparisons were made between those who received packed red blood cell (PRBC) transfusion and those who did not. Primary outcome was hyperkalemia (plasma potassium level >5.5 mmol/L). RESULTS Ninety-six of one hundred thirty-one patients (73.3%) received PRBCs (mean number of PRBC units 11.2, range, 0-55.0). For transfusion versus nontransfusion patients, baseline plasma potassium value (3.7 +/- 0.57 mmol/L vs. 3.6 +/- 0.36 mmol/L, p = 0.22) rose significantly after transfusion (5.3 +/- 1.2 mmol/L, vs. 4.0 +/- 0.78 mmol/L, p < 0.001). During the study period, 38.5% of transfusion patients developed hyperkalemia, versus 2.9% of those who did not (p = 0.003). In multivariate logistic regression analysis, transfusion of greater than 7 units of PRBCs was independently associated with the development of hyperkalemia (RR 4.72, 95% CI 1.01-21.97, p = 0.048). Transfusion of other cell-based products, baseline base deficits, and plasma bicarbonate levels were not. Spearmans rank correlation coefficient for the relationship of number of transfused PRBC units to the highest recorded potassium value was 0.554 (p < 0.001). The predictive accuracy of the logistic regression model for hyperkalemia was 0.824 (95% CI 0.747-0.901, p < 0.001). CONCLUSIONS Hyperkalemia is common after PRBC transfusion, and often severe. PRBC transfusion is independently associated with the development of hyperkalemia. The findings suggest the need for interventional studies examining the impact of alternative resuscitative approaches after severe trauma.

Body mass index and peritoneal dialysis: "exceptions to the exception" in reverse epidemiology?

Until recently, it was not apparent whether apparent paradoxical associations of body mass index (BMI), lipids, and blood pressure with survival observed in hemodialysis (HD) patients, which contradict observations from the general population, also applied to peritoneal dialysis (PD) patients. Studies of survival in PD patients must account for differences in adjusted survival relative to HD patients, namely, early equivalent to superior survival, but after about 1–2 years, inferior survival. Several recent observational studies have analyzed the association between BMI and survival in PD patients from different perspectives and using different patient populations. In general, these studies found that any survival advantage associated with obesity is significantly less likely in PD than HD patients. Among PD patients, those who are obese can be said to have equivalent survival to PD patients with normal BMI. Studies of lipids and blood pressure in PD patients also yield conflicting associations with survival. Obese patients, especially if diabetic, may have increased risk of death after starting on PD compared to HD, although firm conclusions are premature given the limitations of current evidence. At present, the levels of lipids and blood pressure which are best associated with survival in PD patients are not well‐defined.

A descriptive analysis of patients admitted to the intensive care unit of the 10th combat support Hospital deployed in Ibn Sina, Baghdad, Iraq, from October 19, 2005, to October 19, 2006

Background: Although a review of the 1-month experience of a British intensive care unit (ICU) deployed in 2003 to Iraq outlining its care of 47 patients exists, a descriptive study outlining patient characteristics, workload, and outcomes of an ICU during a long-term deployment to Operation Iraqi Freedom is lacking in the medical literature. Methods: Between October 19, 2005, and October 19, 2006, the 10th Combat Support Hospital (CSH) deployed in an ICU to Ibn Sina Hospital in Baghdad, Iraq. Staff prospectively collected patient admission data from November 1, 2005, to August 31, 2006, in handwritten logbooks. This information included nationality (United States/Iraqi/other), military versus civilian, mechanism of injury or nontrauma admission diagnosis, ICU length of stay (LOS), and outcome. These data were retrospectively reviewed for the purpose of reporting the experience of the 10th CSH ICU during its deployment. Results: The 10th CSH ICU admitted 875 patients during the study period. This represented 27% of all hospital admissions (n = 3289). Categories of patients admitted to the ICU included United States military, US contractor, Iraqi military, Iraqi civilian, non-US contractor, coalition military personnel, and security internee. Three patients were unable to be classified due to missing information. The most common patient category of admission was Iraqi civilian (n = 472, 53.9%). Noncoalition (Iraqi civilian, Iraqi military, non-US contractors, and other noncoalition military) admissions made up 76.9% (n = 673) of all admissions. US military (n = 165) and US contractors (n = 31) made up 22.4% of all ICU admissions. Trauma-related admissions were the most common diagnoses (n = 730, 83.4%). Other admission diagnostic categories included medical (n = 125, 14.3%) and postoperative (n = 5, 0.6%) patients. A total of 15 patients (1.7%) were unable to be categorized based on diagnosis due to missing information. The most common medical diagnosis requiring ICU admission was related to cardiovascular disease (n = 51, 40.8%). Seven of the admissions to the ICU were pediatric patients (0.8%). US military personnel traumatically injured suffered significantly more explosion injuries and burns than their Iraqi military and other noncoalition military counterparts. The ICU LOS was significantly shorter in US military and US contractor patients compared to all other groups, likely a result of expeditious air evacuation to a higher level of care. This air evacuation of US personnel combined with the fact that Iraqi patients were transferred to local civilian hospitals prior to the completion of intensive care stay limited follow-up. Despite a lack of meaningful follow-up, the observed ICU all-cause mortality was 5.0% (n = 44). Conclusions:The primary mission of a US military ICU deployed in support of combat operations is the care of its injured troops. However, the 10th CSH deployed in an urban region of Iraq in a mature theater of operations and its ICU more commonly cared for non-US patients during combat medical operations. These patients included pediatric patients as well as admissions for nontrauma illnesses. This mission was accomplished by nurses and physicians faced with unique challenges and resulted in an acceptable ICU mortality rate.

Progressive bevacizumab-associated renal thrombotic microangiopathy

Vascular endothelial growth factor (VEGF) is integral to the integrity of the glomerular filtration barrier. Bevacizumab is a humanized monoclonal antibody directed against VEGF with expanding clinical applications for metastatic solid tumours. We describe a case of a 61-year-old female with ovarian cancer and baseline chronic kidney disease who received three doses of bevacizumab and subsequently developed progressive renal clearance dysfunction and nephrotic range proteinuria. A renal biopsy was performed 4 months after drug discontinuation and was consistent with TMA. At baseline, prior to bevacizumab exposure, her estimated glomerular filtration rate (eGFR) was 44 mL/min/1.73 m2 and she had no proteinuria. At the completion of therapy, eGFR was 27 mL/min/1.73 m2 with 1+ proteinuria on urinalysis. Her renal failure and proteinuria continued to progress 5 months after discontinuation of bevacizumab therapy, at which time eGFR was 11 mL/min/1.73 m2 and proteinuria was 5.5 g/24 h. Non-remitting TMA after bevacizumab therapy in patients with pre-existing chronic kidney disease has not been previously reported. Further studies are needed to assess the safety of this drug in patients with chronic kidney disease.

Renal Replacement Therapy in Austere Environments

Myoglobinuric renal failure is the classically described acute renal event occurring in disaster environments—commonly after an earthquake—which most tests the ingenuity and flexibility of local and regional nephrology resources. In recent decades, several nephrology organizations have developed response teams and planning protocols to address disaster events, largely focusing on patients at risk for, or with, acute kidney injury (AKI). In this paper we briefly review the epidemiology and outcomes of patients with dialysis-requiring AKI after such events, while providing greater focus on the management of the end-stage renal disease population after a disaster which incapacitates a pre-existing nephrologic infrastructure (if it existed at all). “Austere” dialysis, as such, is defined as the provision of renal replacement therapy in any setting in which traditional, first-world therapies and resources are limited, incapacitated, or nonexistent.

CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Body Mass Index and Peritoneal Dialysis: “Exceptions to the Exception” in Reverse Epidemiology?: BODY MASS INDEX AND PERITONEAL DIALYSIS: “EXCEPTIONS TO THE EXCEPTION” IN REVERSE EPIDEMIOLOGY?

Until recently, it was not apparent whether apparent paradoxical associations of body mass index (BMI), lipids, and blood pressure with survival observed in hemodialysis (HD) patients, which contradict observations from the general population, also applied to peritoneal dialysis (PD) patients. Studies of survival in PD patients must account for differences in adjusted survival relative to HD patients, namely, early equivalent to superior survival, but after about 1–2 years, inferior survival. Several recent observational studies have analyzed the association between BMI and survival in PD patients from different perspectives and using different patient populations. In general, these studies found that any survival advantage associated with obesity is significantly less likely in PD than HD patients. Among PD patients, those who are obese can be said to have equivalent survival to PD patients with normal BMI. Studies of lipids and blood pressure in PD patients also yield conflicting associations with survival. Obese patients, especially if diabetic, may have increased risk of death after starting on PD compared to HD, although firm conclusions are premature given the limitations of current evidence. At present, the levels of lipids and blood pressure which are best associated with survival in PD patients are not well‐defined.