To the Editor: In his review of hemodialysis, Ifudu (Oct. 8issue)1 points out the high annual mortality rate of 22 to 24percent among patients undergoing hemodialysis in the UnitedStates and calls for an increase in the dialysis dose. Thisis at odds with the recommendations in Table 1 of the article,in which a Kt/V <1.2 is suggested as being indicative ofinadequate dialysis. (Kt/V is a dimensionless mathematical modelfor quantifying the dialysis dose, where K is the manufacturer'sstated dialyzer urea clearance, t is the length of dialysistreatment, and V is the volume of distribution of urea.) Theaim in the United Kingdom is to increase the adequacy of dialysis,and the Renal Association of the United Kingdom recommends atarget Kt/V in the range of 1.35 to 1.45 in this population.2Indeed, this range represents a minimum, and in general, highertarget values (Kt/V, >1.6) should be used for selected groups,such as younger patients. Similar target values are used inmost of Europe and may in part explain the higher survival ratesand lower rates of comorbidity among European patients on dialysis.. . .
Peter A. Andrews, M.D., M.R.C.P. South West Thames Renal Unit Carshalton,Surrey SM5 1AA, United Kingdom
References
Ifudu O. Care of patients undergoing hemodialysis. N Engl J Med 1998;339:1054-1062. [Free Full Text]
Royal College of Physicians of London. Treatment of adult patients with renal failure: recommended standards and audit measures. 2nd ed. Suffolk, England: Lavenham Press, 1997:17-29.
To the Editor: In his review of the care of patients undergoinghemodialysis, Dr. Ifudu states that "because the hemodialysisregimen is catabolic . . . and amino acids are lost during dialysis,protein intake should be at least 1.5 g per kilogram of bodyweight daily." Consumption of 1.5 g of protein per kilogramper day would provide a 70-kg patient with a total of 105 gof protein. It has been reported that a protein intake of 1g per kilogram per day is more than sufficient to maintain apositive nitrogen balance.1 Several studies have estimated thatapproximately 10 to 15 g of amino acids is lost during a hemodialysissession.2 Dr. Ifudu's recommendation would result in the dailyintake of at least 35 g of protein more than is necessary tomaintain a positive nitrogen balance and significantly morethan what would be lost during a typical hemodialysis session.Therefore, it is puzzling to us why he would suggest such ahigh-protein diet.
The article also suggests the use of a target hematocrit of36 to 40 percent for erythropoietin therapy. This range contrastswith the range of 33 to 36 percent considered appropriate inthe Dialysis Outcomes Quality Initiative guidelines. A recentstudy in the Journal of patients on dialysis who had preexistingcardiovascular disease reported an increased risk of death amongthose with hematocrits of 42 percent, as compared with thosewith hematocrits of 30 percent.3 Until the relation betweenthe management of anemia and the risk of cardiac events is furtherclarified, the value recommended by Dr. Ifudu appears to betoo high.
Anthony Korosi, M.D. Martin Sedlacek, M.D. Elena Slavcheva,M.D. Mount Sinai Medical Center New York, NY 10029
References
Kopple JD, Shinaberger JH, Coburn JW, Sorensen MK, Rubini ME. Optimal dietary protein treatment during chronic hemodialysis. Trans Am Soc Artif Intern Organs 1969;15:302-308. [Medline]
Borah MF, Schoenfeld PY, Gotch FA, Sargent JA, Wolfsen M, Humphreys MH. Nitrogen balance during intermittent dialysis therapy of uremia. Kidney Int 1978;14:491-500. [Medline]
Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998;339:584-590. [Free Full Text]
To the Editor: In his review of hemodialysis, Dr. Ifudu discussesthe management of renal osteodystrophy and states that the intravenousadministration of calcitriol is more efficacious than the oralroute. In cases in which compliance with oral therapy is guaranteedbecause the oral bolus is given under a nurse's supervisionduring the dialysis session, the superiority of the intravenousroute has never been proved. In a recent comparative trial ofthe two routes, Indridason and Quarles1 found that the intravenousadministration of calcitriol resulted in a nonsignificantlygreater suppression of parathyroid hormone, but it was at theexpense of a higher incidence of hyperphosphatemia and hypercalcemia.Another study found that in children with uremia, intravenouscalcitriol was actually less effective in suppressing parathyroidhormone than the same dose given as an oral bolus, despite increasingthe intestinal absorption of calcium to a similar degree.2
Dr. Ifudu also recommends performing a bone biopsy for histologicconfirmation before performing parathyroidectomy, because parathyroidectomymay exacerbate misdiagnosed adynamic bone disease. We quiteagree with this approach, but only for patients who have beenexposed to aluminum, either in the dialysate or through theuse of aluminum phosphate binders. In the absence of such exposure,clinically significant adynamic bone disease is never observedin patients with a plasma intact parathyroid hormone level ofmore than 1000 pg per milliliter, and a bone biopsy is thereforenot necessary.3 Furthermore, the experience of Kaye et al.4shows that in patients who have such high levels of parathyroidhormone but who have not been exposed to aluminum, total parathyroidectomymay have long-term beneficial effects on bone density and bloodphosphate levels.
Albert Fournier, M.D. Philippe Morinière, M.D. AndréPruna, M.D. Centre Hospitalier Universitaire d'Amiens 80054 AmiensCEDEX 1, France
References
Indridason OS, Quarles LD. Prospective randomized trial comparing CaCO3 with oral and intravenous calcitriol in hemodialysis patients with uremic hyperparathyroidism. J Am Soc Nephrol 1997;8:575A-575A.abstract
Ardissino G, Schmitt C, Claris-Appiani A, Dacco V, Mehls O. Equal intestinal calcium absorption and greater pth suppression with oral versus iv calcitriol bolus in children with secondary hyperparathyroidism. J Am Soc Nephrol 1997;8:571A-571A.abstract
Fournier A, Oprisiu R, Hottelart C, et al. Renal osteodystrophy in dialysis patients: diagnosis and treatment. Artif Organs 1998;22:530-557. [Medline]
Kaye M, D'Amour P, Henderson J. Elective total parathyroidectomy without autotransplant in end-stage renal disease. Kidney Int 1989;35:1390-1399. [Medline]
To the Editor: Dr. Ifudu's review of the care of patients undergoinghemodialysis is excellent, but we do not agree with his statement"that renal transplants fare less well in patients who are positivefor hepatitis B or C virus." Although it has been suggestedthat among patients who are positive for hepatitis B surfaceantigen, those who remain on dialysis have a better survivalrate than those who undergo renal transplantation,1 this iscertainly not the case for patients with hepatitis C virus (HCV)infection. Most studies comparing HCV-positive and HCV-negativerenal-transplant recipients have failed to show any differencein patient or allograft survival.2 . . .
Greg Knoll, M.D. Ottawa Hospital Ottawa, ON K1H 8L6, Canada
John Curtis, M.D. University of Alabama Medical Center Birmingham,AL 35294-0007
References
Harnett JD, Zeldis JB, Parfrey PS, et al. Hepatitis B disease in dialysis and transplant patients: further epidemiologic and serologic studies. Transplantation 1987;44:369-376. [Medline]
Pereira BJ, Levey AS. Hepatitis C virus infection in dialysis and renal transplantation. Kidney Int 1997;51:981-999. [Medline]
Dr. Ifudu replies:
To the Editor: I thank my colleagues for their comments. Korosiet al. would limit daily protein intake in patients receivinghemodialysis to about the same amount (0.8 to 1 g per kilogramof body weight per day) recommended for persons with normalrenal function, despite the many factors producing malnutritionin patients on hemodialysis.1,2,3 In addition to the loss ofalbumin and amino acid that occurs during dialysis (exacerbatedby the use of reprocessed dialyzer cartridges, which are nowemployed in the majority of U.S. dialysis facilities1), thesynthesis of albumin is suppressed,3 and metabolic acidosisleads to catabolism of protein as well as oxidation of aminoacids. Also, malnutrition may be worsened by the presence ofelevated serum levels of leptin, which induce early satietyby stimulating the hypothalamus.3
The threshold hematocrit beyond which the risks of correctinganemia outweigh the benefits in patients with end-stage renaldisease is not established. My interpretation of the study byBesarab et al.4 differs from that of Korosi et al.: I do notbelieve that the authors are advocating a target hematocritof 30 percent for all patients on hemodialysis. Other studiesthat assessed outcomes related to the quality of life, as wellas reports of the clinical experience in Europe, have clearlydemonstrated that the outcomes are better and are not associatedwith adverse effects in patients with hematocrits of at least36 percent than in those with hematocrits of 30 percent.5,6
I agree with Dr. Andrews's implication that we should striveto increase the adequacy of dialysis. The limiting factor ischiefly economic constraints. Furthermore, we do not know howmuch dialysis is enough, or whether there is a ceiling dosebeyond which there are no additional benefits.
Fournier et al. are right. Recent randomized clinical trialsfailed to demonstrate any difference in efficacy between intravenousand oral calcitriol when equivalent doses were used. However,though adynamic bone disease may be less likely if the serumparathyroid hormone level is higher than 1000 pg per milliliter,it may be difficult to rule out, on the basis of history taking,past exposure to aluminum in a patient with renal osteodystrophy.
Though HCV infection is not a contraindication to kidney transplantation,Knoll and Curtis oversimplify a controversial issue. Patientswith end-stage renal disease and HCV infection have an increasedrisk of liver disease after transplantation.7 Furthermore, liver-transplantrecipients8 and kidney-transplant recipients9 who are HCV-positiveare more likely to die of liver dysfunction than are HCV-negativetransplant recipients. The inference that hepatitis infectionhas a significant negative effect on survival after kidney transplantationis inescapable.
Two corrections are necessary. The last sentence of the firstfull paragraph in the right-hand column of page 1058 shouldhave read as follows: "The dose of both ethambutol and pyrazinamideshould be reduced in patients on hemodialysis, but the doseof other first-line antituberculosis drugs (rifampin and isoniazid)should not be adjusted." On line 12 of Table 4, the SI valuefor the serum phosphate concentration of 7 mg per decilitershould have been 2.26 mmol per liter.
Onyekachi Ifudu, M.B., B.S. State University of New York HealthScience Center at Brooklyn Brooklyn, NY 11203
References
Kaplan AA, Halley SE, Lapkin RA, Graeber CW. Dialysate protein losses with bleach processed polysulphone dialyzers. Kidney Int 1995;47:573-578. [Medline]
Kaysen GA. Albumin turnover in renal disease. Miner Electrolyte Metab 1998;24:55-63. [CrossRef][Medline]
Johansen KL, Mulligan K, Tai V, Schambelan M. Leptin, body composition, and indices of malnutrition in patients on dialysis. J Am Soc Nephrol 1998;9:1080-1084. [Abstract]
Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998;339:584-590.
Macdougall IC, Ritz E. The Normal Haematocrit Trial in dialysis patients with cardiac disease: are we any the less confused about target haemoglobin? Nephrol Dial Transplant 1998;13:3030-3033. [Free Full Text]
Wells GA, Coyle D, Lee KM, et al. Quality of life effects of normalization of hemoglobin in asymptomatic hemodialysis patients. J Am Soc Nephrol 1998;9:230A-230A.abstract
Periera BJ, Wright TL, Schmid CH, Levey AS. The impact of pretransplantation hepatitis C infection on the outcome of renal transplantation. Transplantation 1995;60:799-805. [Medline]
Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology 1998;28:1687-1695. [CrossRef][Medline]
Hanafusa T, Ichikawa Y, Kishikawa H, et al. Retrospective study on the impact of hepatitis C virus infection on kidney transplant patients over 20 years. Transplantation 1998;66:471-476. [CrossRef][Medline]
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