Polak JF. In: Peripheral Vascular Sonography: A practical Guide. suggests that abnormal BP variation may arise from inhibited. Williams and ... David Goldsmith.
Nephrol Dial Transplant (2000) 15: 131
131
neurofibromatosis type 1. Nephrol Dial Transplant 1999; 14: 1767–1770 2. Krumme B, Rump LC. Colour Doppler sonography to screen for renal artery stenosis—technical points to consider. Nephrol Dial Transplant 1996; 11: 2385–2389 3. Widder B. Bedeutung technischer Kenngro¨ßen der farbkodierten Duplexsonographie fu¨r Gefa¨ßuntersuchungen. Ultraschall Med 1993; 14: 231–239
Reply Sir, We thank Dr Krumme for his thoughtful comments concerning the technical aspects of the renal artery Doppler ultrasound study performed in the hypertensive patient described in our case report [1]. We concur that the Doppler beam angle utilized (71%) was larger than the ideal angle (60°) for accurate calculation of arterial flow velocity. Its upper limits which are suggestive of stenosis are considered to be >150 cm/s [2]. As is often the case however, our patient’s anatomy did not allow acquisition of Doppler U/S data at a lesser angle, without compromising the equally important parallel to the vessel axis direction of the U/S beam. For such cases, it is suggested to utilize 180 cm/s as upper blood flow limit indicative of significant stenosis, obtained with beam incidence angles of up to 80° [2–4], which we actually did. However, irrespective of those technical considerations, the message we were trying to convey to the practicing nephrologist is that essential hypertension is the most frequent cause of elevated arterial blood pressure, especially in patients with neurofibromatosis and in whom the gold standard in diagnosing renal artery stenosis remains selective renal arteriography. Section of Internal Medicine School of Medicine University of Crete Heraklion Crete Greece
E. S. Ganotakis D. Tsetis
1. Vrentzos G, Ganotakis E, Stylianou K et al. Acute angulation of the left renal artery imitating renal artery stenosis in patient with neurofibromatosis type 1. Nephrol Dial Transplant 1999; 14: 1767–1770 2. Stavros T, Harshfield D. Renal Doppler, renal artery stenosis, and renovascular hypertension: direct and indirect duplex sonographic abnormalities in renal artery stenosis. Ultrasound Quart 1994; 12: 217–263 3. Polak JF. In: Peripheral Vascular Sonography: A practical Guide. Williams and Wilkins, 1992: 23. 4. Kaplan-Pavlovcic S, Nadja C. Captopril renography and Doppler sonography in the diagnosis of renovascular hypertension. Nephrol Dial Transplant 1998; 13: 313–317
obtained by one measurement 5 min before a standard HD session. BP variability is a complex series of phenomena [2,3]. Variation can be described over decades (the effect of ageing), over seasons, diurnally, and, on a shorter time-scale, over minutes or even with cardiac systole (LV function and aortic compliance). It is not surprising that comprehensive analysis of these BP variations is notable for its complexity. Using as an index of BP variation a derivative comprising the subtraction of just two BP readings (from a dataset of about 150 readings for each patient taken over a 1 year period ) has the merit of simplicity but may not be robust enough for a study of only 150 patients. What the authors have shown is that patients whose predialysis SBP is more variable (when assessed over 12 months) have a greater all-cause mortality. In their Table 2 it is clear that a greater proportion of the patients with greater-thanmedian SBP variability were older diabetics with lower predialysis BP and plasma creatinine levels. Mortality numbers were really very small—one more patient was withdrawn from dialysis in the higher BP variability group than from the lower group, and one patient died from infection. It is very hard to see how these modes of death are relevant to BP variation, and we suspect that the analysis is only valuable with respect to cardiovascular mortality, and here, once corrected for age, diabetes etc. there was not a significant association. Both uraemia [4] and diabetes [5] are associated with autonomic neuropathy, one of whose manifestations is systolic BP variation with posture. In the discussion the authors state that there was no difference between the higher and lower BP variability cohorts with respect to a disordered autonomic nervous system—but we have failed to spot these data in the paper. Cardiac dysautonomia is a well-recognized marker for cardiovascular mortality [6 ]. Important supportive evidence would bolster the hypothesis—did the patients with greater SBP variability exhibit greater pre-to post-dialysis BP variability, or greater intradialytic BP variability? It was interesting to see that the three cases of fatal congestive cardiac failure were all in the increased BP variation cohort. In our cross-sectional study of the impact of disordered BP variation on cardiac function in haemodialysis patients, we found that the lower the BP variability the larger the left ventricular internal diameter and the worse the LV function [7]. We believe that disordered BP variation is very relevant to patients with all stages of renal disease [8]. A recent paper suggests that abnormal BP variation may arise from inhibited endothelial nitric oxide synthase activity [9] as well as from disordered autonomic function. It is premature we think though to conclude that this has a malign influence on patient survival.
Blood pressure variability measurements
Guy’s Hospital London UK
David Goldsmith Adrian Cork
Sir, The recent article by Tozawa et al. examines the effect of increased variability of systolic blood pressure (SBP) on cardiovascular and all-cause mortality in chronic haemodialysis patients in Japan. The authors report that there was increased all-cause (but not cardiovascular) mortality with higher BP variability [1]. The methods used to measure SBP variation were co-efficient of variation (SD-SBP/Mean SBP×100) and a ‘maximum minus minimum’ SBP value. All BP values were
1. Tozawa M, Iseki K, Yoshi S, Fukiyama K. Blood pressure variability as an adverse prognostic risk factor in end-stage renal disease. Nephrol Dial Transplant 1999; 14: 1976–1981 2. Watson RDS, Stallard TJ, Flinn RM, Littler WA. Factors determining direct arterial pressure and its variability in hypertensive man. Hypertension 1980; 2: 333–341 3. Mancia G, Zanchetti A. Blood pressure variability. In: Zanchetti A, Tarazi RC, eds, Handbook of Hypertension. Vol. 7— Pathophysiology of hypertension: cardiovascular aspects. Elsevier Science Publishers: Amsterdam. 1986; 125–152 4. Hathaway DK, Cashion AK, Wicks MN, Milstead EJ, Gaber
132
5. 6. 7. 8. 9.
AO. Cardiovascular dysautonomia of patients with end-stage renal disease and type I or type II diabetes. Nurs Res 1998; 47: 171–179 Campese VM. Autonomic nervous system dysfunction in uraemia. Nephrol Dial Transplant 1990; 5: 98–101 Barron HV, Viskin S. Autonomic markers and prediction of cardiac death after myocardial infarction. Lancet 1998; 351: 461–484 Covic A, Goldsmith DJA, Georgescu G, Ackrill P. Relationships between BP variability and left ventricular parameters in haemodialysis and renal transplant patients. Nephrology 1998; 4: 87–94 Covic A, Goldsmith DJA. Ambulatory blood pressure monitoring in nephrology—focus on BP variability. J Nephrol 1999; in press Stauss HM, Godecke A, Mrowka R, Schader J, Persson PB. Enhanced blood pressure variability in eNOS knockout mice. Hypertension 1999; 33: 1359–1363
Reply Sir, We wish to provide the following reply to the letter by Dr Goldsmith. There were 194 dialysis patients in our dialysis unit at the start of 1994. Among them, some patients were transferred to other units or died (annual mortality rate was about 10% in all dialysis patients in Okinawa) or transplanted during 1994. After all, complete blood pressure records of a full year of sessions were obtained in only 144 patients (74%). Therefore this study certainly has a bias for survival of patients as mentioned in the last part of discussion [1]. We showed that the difference between the maximum and minimum systolic blood pressure in 1994 (DSBP) correlated with the coefficient of variation in systolic blood pressure (SBPCV ) calculated from 1-year records (about 156 records in each patients) and was an independent predictor for allcauses mortality. We believe DSBP is a reliable index of survival as much as SBPCV. Age, sex, presence of diabetes mellitus, diastolic blood pressure, and serum creatinine were significantly different between the smaller and the larger SBPCV groups ( Table 1 in [1]). Therefore, we adjusted the crude hazard ratios by above clinical variables. Nevertheless, the adjusted hazard ratio of SBPCV and DSBP were statistically significant. The number of deaths was 13 (9.0%) among the studied patients. This was similar to that of the patients in Okinawa, Japan (about 10%). If one includes other dialysis units to
Nephrol Dial Transplant (2000) 15: 132
increase the number of study patients, the bias resulting from inter-dialysis unit data should be taken into account. The hazard ratio of cardiovascular death was not significant. Certainly, we need a longer time of experience to strengthen the evidence or a larger scale investigation. Seasonal variation of blood pressure has been reported in haemodialysis patients [2,3]. We may need to take into account the seasonal variation when evaluating blood pressure variability. The range of seasonal SBP variation was very small (within 2 mmHg) in our study subjects [3]. Also in this study, we used a complete set of blood pressure records throughout the year of 1994 for all the patients. Therefore, the seasonal influence would be negligible in the present study. Dr Goldsmith pointed out that ‘In the discussion, the authors state that there was no difference between the higher and lower BP variability cohorts with respect to a disordered autonomic nervous system.’ In this study, we did not examine the autonomic function of the patients. We only raised the possibility of autonomic disorder with respect to the mechanisms by which blood pressure variability increased the risk of mortality. In our study, we used only pre-haemodialysis BP. Therefore, analyses of pre- to post-dialysis BP variability, or intra-dialytic BP variability have not been done. It is clinically relevant that the mortality from all causes was predicted by the SBPCV or DSBP in this study. Reasons why deaths due to cardiovascular events were not predicted by blood pressure variability remain to be examined in a future study. 1Third Department of Internal Medicine 2Dialysis Unit University of The Ryukyus 3Okinawa Dai-ichi Hospital Okinawa Japan
Masahiko Tozawa1 Kunitoshi Iseki2 Shinichiro Yoshi3 Koshiro Fukiyama1
1. Tozawa M, Iseki K, Yoshi S, Fukiyama K. Blood pressure variability as an adverse prognostic risk factor in end-stage renal disease. Nephrol Dial Transplant 1999; 14: 1976–1981 ` , Mourad G, Mion C. Seasonal changes in blood 2. Argile´s A pressure in patients with end-stage renal disease treated with hemodialysis. N Engl J Med 1998; 339: 1364–1370 3. Tozawa M, Iseki K, Iseki C, Morita O, Yoshi S, Fukiyama K. Seasonal variation of blood pressure and body weight in patients on chronic hemodialysis. Am J Nephrol 1999; 19: 660–667
Letters Contribution of Macedonian nephrologists to the treatment of the renal patients from Kosovo during the recent crisis Sir, Reading the special report entitled ‘International nephrological assistance to Kosovo refugees’ by Professor Norbert Lameire, published in Nephrol Dial Transplant 1999; 14: 1845, we felt inspired to report on our contribution to the assistance of the refugees from Kosovo, who needed renal replacement therapy. During the war in Kosovo, some 250 000 refugees were admitted to Macedonia, a number that far surpassed the capacity of a small country with a population of 2 million.
Among them, 70 patients from the chronic haemodialysis programme of Kosovo came to be treated in our dialysis facilities. The Department of Nephrology from the University of Skopje co-ordinated the distribution of the patients. They were referred to four dialysis centres. Most of the patients (approximately 50) were sent to Struga, the second largest centre in Macedonia, and the rest were dialysed in Tetovo, Gostivar and Debar. The Department of Nephrology also cared for some transplanted patients. Our renal transplant unit provided medical assistance and special care to five patients with renal allografts. Two of them were recent transplants (one transplant in Belgrade and the other in Moscow). For all of them we provided regular outpatient monitoring, continued supply
