Changes in diurnal blood pressure variation and red cell and plasma volumes in patients with renal failure who develop erythropoietin-induced hypertension.

Hypertension is the most common side-effect of treatment with recombinant human erythropoietin (EPO) for the anemia of chronic renal failure. To elucidate why this occurs in some patients we measured changes in blood volumes and diurnal blood pressure (BP) variation during treatment. Isotope labelled measurements of red cell and plasma volume (RCV and PV) were carried out along with ambulatory BP monitoring before starting EPO and after target hemoglobin (Hb) was reached. RCV did not differ between the patient group developing EPO-induced hypertension (EpHT, n = 11) and the group with no change in BP (NC, n = 13) either before or after treatment. However PV was significantly lower in the EpHT group after treatment (2.97 vs 3.92 litres; p < 0.025). Mean BPs differed little between groups because antihypertensive medications were increased as necessary for clinical safety but after achieving target Hb, day-night difference in diastolic BP was greater in the EpHT than the NC group (11.5 vs 4.6 mmHg; p < 0.025) due to a greater rise in daytime BP. There were significant correlations between high day-night diastolic BP differences after EPO in all the studied patients and low plasma volumes either pre- or post-EPO. The study group was heterogeneous but the changes were in the same direction irrespective of type of renal replacement therapy. These results suggest that EPO-induced hypertension is associated with increased daytime vasoconstriction and greater hemoconcentration due to lower plasma volume.

Haemodynamic changes measured by transthoracic bioimpedance during treatment with recombinant human erythropoietin.

Hypertension complicates the treatment of anaemia of chronic renal failure with recombinant human erythropoietin (EPO) in some patients. We conducted a prospective study measuring changes in cardiac index (CI) and systemic vascular resistance index (SVRI) in 29 patients from before commencement of EPO to attainment of target haemoglobin concentration. We used the operator-independent technique of trans-thoracic bioimpedance. The group of patients who developed EPO-induced hypertension (EpHT) were separately analysed and compared with the group who had no change in blood pressure (NC). Our results showed there was a significant rise in SVRI after treatment in EpHT group patients but in the NC group there was a small fall. CI increased significantly in the NC group after treatment but no change was recorded in the EpHT group. These findings clearly demonstrate how the cardiovascular changes differ in patients who develop EPO-induced hypertension.

An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability.

BACKGROUND: Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm itself may be a risk factor for accelerated target organ damage. METHODS: We retrospectively studied 480 ambulatory blood pressure recordings in 380 patients with essential hypertension, secondary hypertension, and on renal replacement therapy. We examined diurnal blood pressure rhythm in each group. RESULTS: Abnormal blood pressure diurnal rhythm (non-dipping) is significantly more prevalent in patients with underlying renal disease, even with normal excretory renal function (53%) than in age-, sex-, and race-matched controls with essential hypertension ((30%), P < 0.01). In patients with renal disease the prevalence of non-dipping rose with worsening renal function, reaching statistical significance once plasma creatinine was greater than 400 mumol/l. There was a direct correlation between plasma creatinine and percent decline in blood pressure at night for both systolic (r = 0.23) and diastolic (r = 0.24) blood pressure in patients with underlying renal disease and impaired excretory renal function. High prevalences of abnormal diurnal BP rhythm are seen in patients on haemodialysis (82%), peritoneal dialysis (78%), patients with plasma creatinine > 600 mumol/l (75%), and in renal transplant recipients (74%). CONCLUSIONS: Abnormal blood pressure diurnal rhythm ('non-dipping') is significantly more common in secondary than in primary hypertension, even with normal renal function. Abnormal blood pressure diurnal rhythm becomes increasingly common with advancing uraemia. Once the plasma creatinine is greater than 600 mumol/l the prevalence of non-dipping is the same as that seen with renal replacement therapy. This phenomenon is not modulated by successful renal transplantation.

Progression of diabetic nephropathy--is diurnal blood pressure rhythm as important as absolute blood pressure level?

BACKGROUND: Hypertensive non-diabetic patients who lack the normal nocturnal decline in blood pressure ('non-dippers') have an increased incidence of cardiovascular complications. Poor blood pressure control is known to exacerbate the decline in glomerular filtration rate in patients with diabetic nephropathy. METHODS: The aim of this study was to assess the contribution of abnormal blood pressure diurnal rhythm to the progression of diabetic nephropathy. We retrospectively studied 26 diabetic patients with hypertension, proteinuria and relentless progressive impairment of renal function due to diabetic nephropathy between 1990 and 1996. Patients underwent ambulatory blood pressure monitoring and were classified as either 'dippers' or 'non-dippers' according to their blood pressure diurnal rhythm. Dippers were patients whose mean sleeping blood pressure (both systolic and diastolic) was 10% less than blood pressure whilst awake. Weight, glycated haemoglobin, serum creatinine (micromol/l) and blood pressure (mmHg) were recorded on a 3-monthly basis. Twenty four hour urine protein excretion and creatinine clearance were recorded annually. The rate of decline of creatinine clearance was derived from serum creatinine estimation. RESULTS: In the 'dipper' group, the rate of decline of creatinine clearance was -2.9 ml/min/year and in those with abnormal blood pressure diurnal rhythm it was -7.9 ml/min/year (P<0.05). There was no significant difference in day-time mean blood pressures, glycated haemoglobin, age and numbers with insulin-dependent diabetes mellitus. CONCLUSION: We found that there was a profound effect of non-dipping upon the rate of decline of renal function in patients with diabetic nephropathy.

How reproducible is diurnal blood pressure rhythm in patients with secondary (renal) hypertension?

Abnormalities (reduction in/absence of) in diurnal bp rhythm are much more commonly seen in patients with chronic uremia than in patients with primary hypertension or in normal subjects. Target-organ damage is greater in these patients. However, the extent to which these diurnal bp rhythm changes are consistent or variable is untested. We retrospectively examined 223 ambulatory blood pressure monitoring (ABPM) traces in 92 patients with chronic uremia who had undergone ABPM at least twice (mean 2.3 ABPM traces/patient) over the period 1991-1997. ABPM technique and analysis were constant over this period. We found that for patients with chronic declining renal function but not yet on dialysis therapy, 67% retained the same diurnal rhythm from one ABPM recording to the next; if the known tendency for declining renal function to accompanied by a greater prevalence of "non-dipping" is taken into account, 82% of all patients had a "predictable" diurnal pattern. 79% of transplant patients, 87% of haemodialysis patients and 100% of CAPD patients retained the diurnal rhythmicity from one ABPM session to the next. Non-dipping was much more frequent than dipping (67% vs 33%). We conclude that abnormalities of diurnal BP rhythm are reasonably consistent in patients with renal hypertension, especially as renal function declines and patients enter the renal replacement therapy programme.