Extended daily dialysis vs. continuous hemodialysis for ICU patients with acute renal failure: a two-year single center report.

Extended daily dialysis (EDD) is an easily implemented alternative to continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). Since EDD offers most of the advantages of CRRT, we sought to compare the effectiveness of these two modalities. In this 2-year study, 54 ICU patients with ARF were treated with either continuous hemodialysis (CHD) or EDD. Oliguria was present in 64% of patients who received CHD vs. 73% of EDD patients (p=NS) while 93% of CHD and 81% of EDD patients required mechanical ventilation (p=NS). Patients treated with EDD were younger than those who received CHD (47.0 +/- 12.6 vs. 56.7 +/- 13.7, p=0.009), but there were no significant differences in gender or mean APACHE II scores at the time of randomization. Mean arterial blood pressures measured during treatment were maintained between 70 and 80 mmHg for both EDD and CHD and average daily serum electrolyte levels fell within normal ranges for EDD and CHD. Average daily fluid input and output were 5.8 +/- 3.3 L and 6.0 +/- 3.2 L for CHD vs. 3.3 +/- 2.6 and 3.0 +/- 1.7 L for EDD after exclusion of data from 2 burn patients. Hourly heparin anticoagulation rates were 1080 U/hour for CHD and 643 U/hour for EDD, p=0.02. Anticoagulation-free treatments were performed during 43% of all EDD treatments vs. 21% of all CHD treatments, p<0.001. Clotting of the dialyzer or circuit occurred at least once during 51% of all CHD treatment days vs. 22% of EDD treatments (p<0.001). We conclude that EDD is a safe, effective alternative to CRRT that offers comparable hemodynamic stability and excellent small solute control.

Initial therapy for uncomplicated hypertension: insights from the alphabetic maze of recent studies.

Some hypertension treatment guidelines published in the late 1990's recommended that diuretics and betha-blockers be used as 1st line drugs for treating uncomplicated hypertension, reserving new antihypertensive drugs for special indications. This recommendation is predicated on the fact that large trials showing cardiovascular protection with antihypertensive drugs used betha-blockers and diuretics. Other guidelines suggested all antihypertensives are equal and that drug selection should be individualized. These disparate guidelines arise from the controversy over "are all antihypertensives created equal?" Since these guidelines, many large hypertension trials have been conducted. This paper will review the recent hypertension trials, the meta-analyses of some of these trials, highlight some of the flaws inherent in the trials that making interpretation difficult, and finally outline a rationale approach to initial treatment of the uncomplicated hypertensive patient. It will provide a rationale for 1) using diuretic and not beth-blocker as the 1st line agent in treating uncomplicated hypertension, 2) switching to an angiotensin converting enzyme inhibitor or angiotensin receptor blocker should side effects occur on diuretic, 3) reserving calcium channel blocker, betha-blocker, and alpha-blocker for 2nd or 3(rd) line therapy, 4) employing a diuretic in combination with any other antihypertensive class, and 5) considering use of lower doses of 2 or more antihypertensives to limit side effects while optimizing blood pressure control. If the incidence of de novo diabetes is indeed higher with diuretics and cost-analysis confirm long-term savings with using a more expensive but less diabetogenic drug to treat hypertension, then the recommendation may shift to using an antihypertensive that acts on the renin-angiotensin axis.

Initial antihypertensive therapy. What are the current drugs of choice?

The goal of antihypertensive treatment, in addition to lowering blood pressure, is to reduce the risk of cardiovascular events. Until recently, however, only conventional treatment with diuretics and beta-blockers had been studied in terms of cardiovascular end points. In this article, Dr Yeun reviews the results of recent trials comparing these agents with other classes of antihypertensive drugs. She examines the confounding elements in the trials, provides an interpretation of study results, and suggests a practical approach to initial treatment of uncomplicated hypertension.

C-reactive protein, oxidative stress, homocysteine, and troponin as inflammatory and metabolic predictors of atherosclerosis in ESRD.

Mortality in patients with end-stage renal disease remains high, with cardiovascular disease accounting for half of these deaths. Novel risk factors such as inflammation, oxidative stress, hyperhomocysteinemia, and high troponin levels are associated with cardiovascular risk in the general population. While there are substantial epidemiologic data confirming that these novel risk factors are associated with cardiovascular risk in end-stage renal disease patients, a causal relationship has not been established. Inflammation is readily identified by the presence of high levels of C-reactive protein, while studies of oxidative stress are hampered by the lack of a standardized test. The cause of both is unknown. Hyperhomocysteinemia results from decreased remethylation to methionine, although vitamin supplementation only partially corrects the defect, suggesting that uremic inhibition of the enzymatic process may be important. The most promising strategies for correcting oxidative stress and hyperhomocysteinemia are vitamin E and folinic acid therapy, respectively. Troponin I appears to be a more specific marker of myocardial injury than Troponin T, but troponin T retains its ability to predict cardiovascular mortality as well as all-cause mortality. Sorting out the role of each of these risk factors may be difficult since the factors may influence each other, may increase oxidative stress, and may mediate atherosclerosis through oxidative modification of lipids.

Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit.

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients.

Hypoalbuminemia predicts death in dialysis patients. Although hypoalbuminemia has been attributed to malnutrition, evidence of inflammation (C-reactive protein [CRP] and cytokine levels) has recently been recognized to predict albumin concentration in dialysis patients. We measured CRP and albumin levels in October 1995 in 91 hemodialysis (HD) patients. During a 34-month follow-up period, we determined the incidence and cause of death. Patients were divided into four groups based on serum albumin levels (<3.5 [lowest quartile], 3.5 to 3.8, 3.9 to 4.0, and >4.0 g/dL [highest quartile]). Survival differed among the four groups (P = 0.0063). Patients with albumin levels greater than 4.0 g/dL had the greatest survival. Kaplan-Meier survival estimates of patients from varying CRP quartiles (<2.6, 2.6 to 5.2, 5.3 to 11.5, and >11.5 microg/mL) differed among the four groups (P < 0.0001). The group with the greatest CRP level (>11.5 microg/mL) had the lowest survival. Multivariate analysis using the Cox proportional hazards model showed that only CRP level (chi-square = 21.11; P < 0.0001) and age (chi-square = 5.44; P = 0.020) predicted death. Albumin level (chi-square = 0.16; P = 0.69) was not predictive. Only when CRP was excluded from the model did low serum albumin level (chi-square = 12. 04; P = 0.0004) predict death. CRP level (chi-square = 16.79; P < 0. 0001) and age (chi-square = 6.38; P = 0.012) also superceded albumin level (chi-square = 0.45; P = 0.51) in predicting cardiovascular mortality. Although values for blood urea nitrogen, creatinine, and normalized protein catabolic rate were significantly less among patients who died, these parameters, as well as cholesterol level and diabetes, were not important predictors of death in multivariate analysis. The acute-phase response or the cause of the acute-phase response is largely responsible for the effect of hypoalbuminemia on mortality in HD patients.

Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients.

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.

Factors influencing serum albumin in dialysis patients.

Hypoalbuminemia is a major risk factor for morbidity and mortality in dialysis patients. The proximate cause of hypoalbuminemia is probably responsible for these events, and not the hypoalbuminemia itself. Because protein-calorie malnutrition decreases albumin synthesis, hypoalbuminemia has been attributed to poor nutritional intake resulting from underdialysis. However, serum albumin (Salb) level is determined by several other factors: plasma volume expansion, albumin redistribution, exogenous loss, increased fractional catabolic rate (FCR), and decreased synthesis. Decreased albumin synthesis is primarily responsible for hypoalbuminemia in hemodialysis (HD) patients. Studies of a smaller number of peritoneal dialysis (PD) patients suggest exogenous albumin loss and volume expansion as contributing mechanisms. However, both malnutrition and inflammation suppress albumin synthesis. As the adequacy of dialysis has improved, recent studies are unable to show any relation between dialysis adequacy and Salb level. Further, Salb level appears to be a poor marker of nutritional status in dialysis patients when compared with other measures of nutrition, such as subjective global assessment score, anthropometry, and dietary intake. Instead, cytokines and positive acute-phase reactants, produced in response to inflammation, have been identified as important contributors to hypoalbuminemia in dialysis patients. These markers correlate with hypoalbuminemia and supercede Salb level in predicting mortality. Multivariate analysis identifies markers of inflammation and nutritional status as independent predictors of hypoalbuminemia in HD patients and markers of inflammation and peritoneal albumin loss as independent predictors in PD patients. However, the acute-phase response and malnutrition are closely interrelated, because inflammatory mediators also suppress appetite, increase muscle catabolism, and result in progressive cachexia. Future studies should focus on elucidating the inflammatory stimuli and the complex interaction between the acute-phase response and nutritional status.

Acute phase proteins and peritoneal dialysate albumin loss are the main determinants of serum albumin in peritoneal dialysis patients.

Hypoalbuminemia predicts mortality in dialysis patients. It has been postulated that hypoalbuminemia in the dialysis population is a consequence of poor protein intake resulting from inadequate dialysis. To establish the cause of hypoalbuminemia in a group of 27 patients on peritoneal dialysis (PD), we determined the relationship between serum albumin concentration and a group of parameters including dialysis dose delivered (Kt/V), normalized protein catabolic rate (PCRn), transperitoneal and urinary albumin losses, and the serum concentration of two acute-phase proteins, C-reactive protein (CRP), and serum amyloid A (SAA). Serum albumin concentration could be predicted by a combination of transperitoneal albumin loss and either the serum concentration of CRP or of SAA. There was no relationship between weekly Kt/V or PCRn and serum albumin concentration. CRP and SAA significantly correlated with one another, but neither correlated with transperitoneal albumin losses. Hypoalbuminemia in PD patients is a consequence of transperitoneal albumin losses and of the acute phase response.

Chronic calcium pyrophosphate crystal deposition disease arthropathy associated with hypomagnesemia.

We describe a case of a young woman with a magnesium renal wasting syndrome leading to severe hypomagnesemia and a chronic pseudo-osteoaritis calcium pyrophosphate crystal deposition disease (CPDD) arthropathy. A chronic CPDD arthropathy secondary to hypomagnesemia has not been previously reported. The identification of CPDD, particularly in the young, can be a clue to the presence of a potentially treatable underlying metabolic disorder, such as hypomagnesemia.

Renal hypouricemia: prevention of exercise-induced acute renal failure and a review of the literature.

Isolated renal hypouricemia from defective uric acid reabsorption and/or secretion is a well-described entity, with a prevalence of 0.12% to 0.20% in Japan. It is rarely associated with exercise-induced acute renal failure (ARF). The etiology of ARF is debated. Prevention of ARF in renal hypouricemia has not been previously addressed. A 29-year-old Pakistani man had recurrent exercise-induced ARF. He was found to have isolated renal hypouricemia; serum uric acid 0.5 mg/dL, 24-hour urine uric acid 472 +/- 25 mg (+/- SD), and fractional excretion of uric acid 55.2% to 69.4%. Both pyrazinamide and probenecid decreased fractional excretion of uric acid and uric acid excretion rate (UV(Urate)) in our patient, suggesting either a partial presecretory and postsecretory reabsorption defect or increased secretion. We investigated renal uric acid excretion during exercise in our patient and four control subjects. All five subjects underwent a physical fitness test (PFT). Our patient developed ARF. Uric acid excretion rate increased in our patient, from 0.48 mg/min at baseline to 1.49 mg/min 4 hours after the PFT, as did the urine uric acid to urine creatinine ratio (UUa)/UCr) (0.29 to 1.49). In the controls, UV(Urate) and UUA/UCr were unchanged after the PFT: UV(Urate) was 0.46 +/- 0.10 mg/min at baseline and 0.59 +/- 0.04 mg/min 4 hours after the PFT, while UUA/UCr was 0.30 +/- 0.04 at baseline and 0.36 +/- 0.04 at 4 hours. All five subjects took allopurinol 300 mg daily for 5 days and repeated the PFT. In our patient, allopurinol prevented the ARF as well as the exercise-induced increases in UV(Urate) (0.28 mg/min to 0.22 mg/min) and UUA/UCr (0.25 to 0.17). In the controls, the UV(Urate) and UUA/UCr responses to exercise were not altered. We conclude that increased renal excretion of uric acid during exercise was responsible for the ARF in our patient with renal hypouricemia and that successful prophylaxis with allopurinol is possible.

Pneumoperitoneum in peritoneal dialysis patients.

There has been recent controversy regarding the clinical significance of pneumoperitoneum in patients undergoing peritoneal dialysis. The incidence of pneumoperitoneum has been estimated to be 21.2% to 33.7% in prior studies of peritoneal dialysis patients. Of the peritoneal dialysis patients with pneumoperitoneum, only a small percentage (5.9% to 14.3%) had documented visceral perforations. The controversy arises in that anywhere from 20% to 100% of peritoneal dialysis patients with pneumoperitoneum and peritonitis had visceral perforation, and 32.4% to 57.1% of chronic ambulatory peritoneal dialysis patients had asymptomatic pneumoperitoneum of unknown etiology. These disparate incidences made clinical interpretation of pneumoperitoneum difficult. In addition, prior study result disagreed as to the usefulness of the extent of pneumoperitoneum in predicting visceral perforation. We retrospectively reviewed 694 chest x-ray film and acute abdominal series reports from 1982 to 1993 in 75 peritoneal dialysis patients, with 9.3 +/- 1.3 (mean +/- SEM) x-ray films per patient. The reports were confirmed by reviewing 363 x-ray films (52%). Eight patients (10.7%) had 10 episodes of pneumoperitoneum. Six of these eight patients had asymptomatic pneumoperitoneum from a known etiology: four had undergone abdominal surgery for catheter placement the prior week and two had catheter manipulation immediately preceding the x-ray. One patient had three episodes of pneumoperitoneum: one after catheter placement and two not associated with a known etiology for pneumoperitoneum while on the cycler. One patient had a surgically confirmed colonic perforation with a large pneumoperitoneum and peritonitis.(ABSTRACT TRUNCATED AT 250 WORDS)