James T. McCarthy

Prognosis of Patients With Acute Renal Failure in the Intensive-Care Unit: A Tale of Two Eras

OBJECTIVE To determine whether any changes occurred in the complexity of illness or survival of Mayo intensive-care unit (ICU) patients with acute renal failure (ARF) who required hemodialysis between the 1977 through 1979 period and the 1991 and 1992 era. DESIGN A retrospective comparison was done of 71 consecutive ICU patients with ARF during 1977 through 1979 and 71 similar consecutive patients from the 1991 and 1992 period. MATERIAL AND METHODS Each patient was scored for the three components of the acute physiology and chronic health evaluation (APACHE) II system (acute physiology score, age, and preexisting chronic health problems). Patient gender, postoperative status, presence of diabetes mellitus, presence of chronic renal insufficiency, and factors contributing to ARF were recorded for each patient. Patient survival and renal function at time of hospital dismissal and 12 months after initiation of hemodialysis were determined. RESULTS In comparison with patients in the earlier study period, those in the later study period had a signficantly improved rate of hospital survival (52% versus 32%) and 1-year survival (30% versus 21%). At 1 year, 96% and 78% of survivors in the earlier and later study groups, respectively, had recovery of renal function. The mean total APACHE II score was the same in both study periods, but patients in the later group were older and had more APACHE II points for chronic health problems. In the earlier and later study groups, patients with an APACHE II score of 21 or lower had a mortality rate of 36% and 11%, respectively, and survival among those with a score of 34 or greater was 0% and 15%, respectively. In 1991 and 1992, more patients had two or more factors contributing to the development of ARF, and intravenous administration of a contrast agent and preexisting cardiac prerenal compromise were more frequent causes of ARF than in 1977 through 1979. The occurrence of sepsis and preexisting lung disease were associated with a dismal prognosis in both study periods. In 1991 and 1992, survival was improved for patients with preexisting diabetes mellitus, postoperative status, and contrast-induced renal failure. CONCLUSION The prognosis of ICU patients with ARF has improved in more recent years, despite the fact that patients are now older, have more preexisting chronic health conditions, and have an increasing number of conditions contributing to development of ARF. The APACHE II scoring system demonstrated utility for quantifying the complexity of illness in these patients, but several important shortcomings may limit its usefulness as a comparative or prognostic tool in patients with ARF.

Long-term fracture risk following renal transplantation: a population-based study

Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965–1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject’s complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected (P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6–6.4] and vertebral (SIR, 23.1; 95% CI, 12.3–39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1–12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.

The Effects of Sevelamer and Calcium Acetate on Proxies of Atherosclerotic and Arteriosclerotic Vascular Disease in Hemodialysis Patients

Background: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. Methods: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. Results: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate –2.5 ± 1.8 mg/dl vs. sevelamer –2.8 ± 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium ≧10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 ± 2.1 g/day – equivalent to 1.2 ± 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 ± 350, median change +20, p = 0.002) and aorta (mean change 181 ± 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. Conclusion: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.

Infective Endocarditis in Patients Receiving Long-term Hemodialysis

OBJECTIVE To ascertain the predominant characteristics of patients receiving long-term dialysis who develop infective endocarditis (IE). PATIENTS AND METHODS We reviewed the records of all chronic hemodialysis patients who had IE at Mayo Clinic, Rochester, Minn, between 1983 and 1997. RESULTS Twenty episodes of IE occurred in 17 patients. One patient had 3 episodes of IE, and 1 patient had 2 episodes of IE; each episode was caused by a different organism. The mean +/- SD age of our patients was 63 +/- 11 years; there were 13 males; 6 patients had diabetes mellitus; and the mean +/- SD duration of hemodialysis prior to IE was 24.2 +/- 20.5 months. This analysis included 10 episodes of IE (occurring in 9 patients) within the Mayo Clinic Dialysis System during which time 223,358 hemodialysis treatments were delivered, giving a rate of 10 IE episode per 223,336 hemodialysis treatments. Among all 20 IE episodes, there were 14 synthetic arteriovenous grafts, 4 permanent venous dialysis catheters, 2 temporary venous dialysis catheters, and 2 native arteriovenous fistulas (2 accesses in 2 patients), and access had been in place for a mean +/- SD of 15.9 +/- 18.6 months. The portal of infection was the hemodialysis access in 13 episodes of IE. The causative organisms for IE were Staphylococcus aureus in 8 cases, Enterococcus sp in 4 cases, viridans streptococcus in 3 cases, Staphylococcus epidermidis in 2 cases, and 1 case each of Streptococcus bovis, group G beta-hemolytic streptococcus, and Aspergillus sp. The mitral valve was involved in 9 cases, the aortic valve was involved in 5 cases, and the tricuspid and pulmonic valves were involved in 1 case each. Patient survival (after the first episode of IE) was 71% at 30 days; 53% at 60 days; and 35% at 1 year. Echocardiography was performed in 19 episodes of IE. The transthoracic echocardiogram was 62.5% sensitive and 40% specific for the presence of definite or probable vegetations. Univariate analysis for factors affecting 60-day survival show that presence of right-sided IE, vegetation size greater than 2.0 cm3, diagnosis of diabetes mellitus, and initial leukocyte count greater than 12.5 x 10(9)/L were poor prognostic factors. Aortic valve involvement carried a better prognosis. CONCLUSIONS Infective endocarditis in hemodialysis patients is relatively infrequent but has a high mortality. Patients with synthetic intravascular dialysis angioaccess (synthetic grafts and venous catheters) are more likely to develop IE than patients with native arteriovenous fistulas. Transesophageal echocardiography is a preferred echocardiographic study for suspected cases of IE. Prolonged antibiotic therapy is needed for all patients, and close monitoring is needed for patients with right-sided IE, large vegetations, diabetes mellitus, and an elevated leukocyte count.

Effect of Daily Hemodialysis on Depressive Symptoms and Postdialysis Recovery Time: Interim Report From the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study

BACKGROUND Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. STUDY DESIGN The FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. SETTING & PARTICIPANTS Adult patients initiating daily HD with a planned 12-month follow-up. OUTCOMES & MEASUREMENTS The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. RESULTS 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 [95% CI, 9.6-12.9] vs 7.8 [95% CI, 6.5-9.1]; P<0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score>10) significantly decreased during 12 months (41% vs 27%; P=0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 [95% CI, 359-594] vs 63 minutes [95% CI, 32-95]; P<0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (>or=60 minutes) also significantly decreased (81% vs 35%; P=0.001). LIMITATIONS Observational study with lack of control arm. CONCLUSIONS Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.

Outcomes of Arteriovenous Fistula Creation after the Fistula First Initiative

BACKGROUND AND OBJECTIVES The arteriovenous fistula (AVF) is the preferred hemodialysis access, but AVF-failure rate is high, and complications from AVF placement are rarely reported. There is no clear consensus on predictors of AVF patency. This study determined AVF outcomes and patency predictors at Mayo Clinic Rochester following the Fistula First Initiative. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A retrospective cohort study of AVFs placed at Mayo Clinic from January 2006 through December 2008 was performed. The AVF placement-associated primary and secondary failure rates, complications, interventions, and hospitalizations were examined. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine primary and secondary patency and associated predictors. RESULTS During this time frame, 317 AVFs were placed in 293 individual patients. The primary failure rate was 37.1% after excluding patients not initiated on hemodialysis during follow-up (n = 38) or those with indeterminate outcome (37 lost to follow-up; six died; two transplanted). Of usable AVFs, 11.4% later failed. AVF creation incurred complications and hospitalization in 21.2% and 12.3% of patients, respectively. The risk for reduced primary patency was increased by diabetes (HR, 1.54; 95% CI, 1.14 to 2.07); the risk for reduced primary and secondary patency was decreased with larger arteries (HR, 0.83; 95% CI, 0.73 to 0.94; and HR, 0.69; 95% CI, 0.56 to 0.84, respectively). CONCLUSIONS Primary failure remains a major issue in the post-Fistula First era. Complications from AVF placement must be considered when planning AVF placement. Our data demonstrate that artery size is the main predictor of AVF patency.

Improved Biochemical Variables, Nutrient Intake, and Hormonal Factors in Slow Nocturnal Hemodialysis: A Pilot Study

OBJECTIVE To determine whether slow nocturnal hemodialysis (SNHD) can be safely performed in patients with end-stage renal disease to improve the biochemical and clinical outcome. MATERIAL AND METHODS We conducted an 8-week pilot study in nondiabetic adult patients, who underwent dialysis 6 nights per week for 8 hours each night. A dialysate flow rate of 300 mL/min and a blood flow rate of 250 mL/min, through an internal jugular dual-lumen venous catheter, were used. The equipment used was a COBE Centry System 3 dialysis machine and Fresenius F-80 (1.8 m2) or Baxter CT 190 (1.9 m2) dialyzers. Five patients were enrolled in the study. RESULTS Two patients did not complete the study because of catheter-related infections--one at day 7 and one after 4 weeks of SNHD. All patients had improved blood pressure control, and no intradialytic adverse events occurred. Dietary intake improved, urea and creatinine levels significantly decreased, and weekly delivery of dialysate increased on SNHD. Potassium, chloride, beta 2-microglobulin, phosphorus, calcium, and high-density lipoprotein cholesterol all improved on SNHD. Serum testosterone increased in the three men on SNHD, but parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone remained unchanged. Erythropoietin levels increased on SNHD, despite no change in exogenous erythropoietin doses in three patients and discontinuation of administration of erythropoietin in one. The following biochemical factors did not change significantly: serum sodium, bicarbonate, vitamin B12, folate, alkaline phosphatase, total cholesterol, triglycerides, and albumin. CONCLUSION Higher doses of hemodialysis benefit nutrition, improve biochemical variables, and may improve many hormonal systems.

Results of subtotal parathyroidectomy in hemodialysis patients

In 61 hemodialysis patients undergoing subtotal parathyroidectomy, there was a good correlation between the preoperative serum immunoreactive parathyroid hormone value (iPTH) and the weight of parathyroid tissue removed surgically (p less than or equal to 0.001). Postoperatively, iPTH decreased rapidly from an initial mean (+/- SD) of 2,928 +/- 1,600 muleq/ml and remained at 365 +/- 296 muleq/ml at last follow-up of patients still undergoing hemodialysis (normal, less than 50 muleq/ml). Of six patients who had recurrent hyperparathyroidism (10 percent of total), three required a second subtotal parathyroidectomy. Aluminum-related osteomalacia eventually developed in six patients with bone biopsy-proven hyperparathyroidism before parathyroidectomy. Nine patients with severe fracturing bone disease and hypercalcemia preoperatively but without clear evidence of hyperparathyroidism did not show a favorable response to subtotal parathyroidectomy (high mortality within 28 months, persistence of hypercalcemia, and symptomatic bone disease). Thus, subtotal parathyroidectomy can benefit patients with clearly established severe progressive hyperparathyroidism not responsive to medical therapy but is contraindicated in patients with low iPTH values and no bone biopsy evidence of severe hyperparathyroidism.

Fulminant Wilson's disease treated with postdilution hemofiltration and orthotopic liver transplantation

A 22-yr-old woman presented with fulminant Wilsons disease. The diagnosis was suspected clinically and was later confirmed with chemical and pathologic studies. She presented with acute hepatic failure, hemolysis, and acute anuric renal failure. Postdilution hemofiltration and continuous arteriovenous hemofiltration with oral D-penicillamine allowed removal of a total of 95,700 micrograms of copper; 78,665 micrograms of the total were removed via postdilution hemofiltration alone. On the 57th day, the patient received successful liver and renal transplants. We found that the determination of serum copper was instrumental in the diagnosis of fulminant Wilsons disease, that postdilution hemofiltration allowed a rapid removal of copper in the presence of renal failure, and that, finally, orthotopic liver transplantation should be performed early in the clinical course of these patients. This patient is the longest survivor of this serious condition.

Improved preservation of residual renal function in chronic hemodialysis patients using polysulfone dialyzers

Our objective was to determine whether patients with chronic renal failure requiring maintenance hemodialysis retain intrinsic renal function longer when using reprocessed polysulfone (PS) membrane hemodialyzers or single-use cellulose acetate (CA) membrane hemodialyzers. Fifty consecutive patients with residual renal function (urea clearance > 2.0 mL/min) using PS dialyzers were compared with a retrospective, disease- and time-matched population of patients using CA dialyzers. Endogenous urea clearance was measured every 3 months in all patients with remaining residual function. Other data collected included age, sex, cause of chronic renal failure, use of angiotensin-converting enzyme inhibitors or calcium channel blockers, and hemodynamic stability during hemodialysis. All patients were observed for at least 6 months while using a single type of dialyzer. Study end points included loss of residual renal function (urea clearance < 1.0 mL/min), death, transplant, transfer to peritoneal dialysis, or change of dialyzer. The PS and CA groups of patients were well matched for sex, age, initial renal clearance, predialysis blood pressure, and hemodynamic stability during hemodialysis. The PS patients had a higher delivered Kt/V (1.34 +/- 0.30 [mean +/- SD]) than the CA patients (1.06 +/- 0.20). The PS group had a higher average urea clearance than the CA group after 4 to 9 months of dialysis (2.8 +/- 2.6 mL/min v 1.7 +/- 1.6 mL/min, respectively), after 10 to 15 months of chronic dialysis (2.0 +/- 2.4 mL/min v 1.1 +/- 1.5 mL/min, respectively), and after 16 to 21 months of dialysis (1.3 +/- 1.9 mL/min v 0.5 +/- 1.1 mL/min, respectively; all P < 0.03, t-test). After 22 to 24 months of dialysis, the difference between the two groups was not significant. When comparing patients with identical causes of chronic renal failure, there were no differences between the PS and CA groups for those with diabetes mellitus, tubulointerstitial disease, or polycystic disease. Patients with parenchymal renal disease (glomerulonephritis or nephrosclerosis) had markedly better retention of intrinsic renal function with PS than with CA dialyzers (all P < 0.01). Kaplan-Meier analysis for retention of intrinsic renal function showed that PS patients with parenchymal renal disease had a mean of 23 months before loss of intrinsic renal function, whereas for CA patients the mean was 11 months before loss of intrinsic renal function (P = 0.0005). Cellulose acetate patients lost renal function at an average rate of 0.27 +/- 0.22 mL/min/mo, whereas for PS patients the rate was 0.14 +/- 0.56 mL/min/mo (P = 0.06, rank sum). CA patients with parenchymal renal disease lost renal function at a rate of 0.29 +/- 0.22 mL/min/mo, whereas for PS patients the rate was 0.0 +/- 0.8 mL/min/mo (P = 0.004, rank sum). Age, sex, and the use of either angiotensin-converting enzyme inhibitors or calcium channel blockers did not have an effect on the loss of intrinsic renal function. Patients with nondiabetic parenchymal renal disease receiving chronic hemodialysis with hydrogen peroxide/peroxyacetic acid-reprocessed PS dialyzers and a higher Kt/V lose residual renal function at a slower rate than disease-matched patients using single-use CA dialyzers. Our findings provide further evidence that the choice of dialyzer membrane may have an effect on intrinsic renal function.