INFLUENCES OF ARTERIAL HYPERTENSION ON THE PROGNOSIS OF URAEMIC PATIENTS UNDERGOING HAEMODIALYSIS
A study of 90 CRF patients, admitted during the period March 1997 to March 1999.

Dr. Saeed Mhamed Alwan Abdullah
Internist, and Senior Lecturer at Aden Medical Faculty.

Haemodialysis center. Al Gamhouria Teaching Hospital.
Aden-Mansoura. Yemen

dr.salwan@yemen.net.ye

Further approach to uraemic on dialysis patients at HD center Aden is needed to study different influences that may have important contribution in this elevated mortality rate rather than the high BP.

Introduction

In 1773 urea was first isolated from human urine by Rouelle, and in 1800s Fourcroy coined the term "uree"to avoid confusion with urinque "uric acid".

In 1827 Richard Bright a pioneer in this field, observed the accumulation of the urea in the blood of the patients with dropsy and he linked it with decreased urinary urea and diseased kidney and in 1830, he described the association of high blood pressure with LVH in patients dying of renal failure. The term uremia was first coined in 1840 by Priorry, to indicate "contaminating blood with urine". Uremia is a complex condition with characteristic features resulting from renal failure, which causes accumulation of unexcreted waste products. Thus not all patients with renal failure are uraemic. This distinction is important, because uremia is an indication of dialysis.

Late in the nineteenth century, Hahomet Albutt, and Von Basch discarded the previous original observations that arterial hypertension was a condition associated exclusively with renal diseases, and confirmed that hypertension produced LV changes and blood vessels abnormalities, in a patients dying without evidence of severe renal disease.

In 1903, Strauss, introduced blood urea as a diagnostic test for renal diseases¹, and finally in 1931 Jolliffe and Smith introduced the concept of creatinine clearance for practical application. Virtually all renal diseases are associated with increased incidence of high blood pressure, the kidney is also one of its principle target. Hypertension occurs in approximately 80% to 90% of uremia patients before the initiation of dialysis^2,3. The importance of volume expansion is evident from studies that demonstrate control of hypertension in about 60% to 70% of the patients, simply by reduction of extracellular volume with utrafiltration during HD (volume responsive)^3,4,5. The remainder has sustained high BP with Euvolumic State or become more hypertensive with fluid removal (volume unresponsive, renine dependent)⁶.

In 1992 in Tassin France, Charra, et. al. Studied a group of a dialysis patients, clarified that the longevity was attributed to excellent blood pressure BP control. In European dialysis and transplantation association EDTA registry 10 years mortality was increased by 30% in patients with a mean arterial pressure (MAP) greater than 99 mmHg^6,7.

MAP fail to correlate inversely with survival in some dialysis patient registries, with higher mortality also found in patients with very low BP, many of them have severe cardiovascular diseases⁸.

The pathophysiology of uremic hypertension in patients undergoing HD has been well characterized, and include the following factors^5,6,9,10:

• Endothelin (endothelium constricting factor)
• The sympathetic nervous system is activated in uremia.
• Volume dependent hypertension.
• Renine dependent hypertension.
• Preexisting or coexisting condition (systemic lupus erythematous SLE, high BP).

Arterial hypertension and its complications (LVH, and LVF) are the most important survival determinant in dialyzed patients, and at same time they are more amenable to treatment^{11 12,}. Left ventricular dysfunction is the most common heart abnormality found in dialyzed patients and associated strongly with premature death, arrhythmia and dialysis hypotension, with high mortality rate among these groups^12,13,14,15. It is clear that controlling BP can arrest or even reverse the LV dysfunction^6,16,17.

General objective
To study the incidence of arterial hypertension and its complications, in uremic haemodialyzed patients, and their influences on the mortality of these patients.

Specific objective

• To estimate the incidence of arterial hypertension in HD patients.
• To recognize the influence of arterial hypertension on the mortality rate of uraemic haemodialyzed patients.
• To recognize the most serious complications (with fatal outcome) of high BP in HD patients.
• To evaluate the influence of volume status (mainly overload) on the rising BP.
• To recognize the importance of achieving the dry weight (by volume removal through Ultrafiltration UF during HD), in controlling the hypertension in dialysis patients.
• To know the influence LVH, and LVF (as hypertensive organ damage) in the prognosis of these patients.

Material and Methodology

This is prospective study of the first (90) patients admitted to medical ward through casualty department since the inauguration of haemodialysis center at Al Gamhouria teaching hospital ATH in March 1997. They were emergency cases of uremia with urgent indication of HD. These cases were followed up through the period from March 1997 to March 1999.

As our research is only concerned with chronic HD, 12 patients were excluded because of the following reasons:

Ten (10) patients were admitted with acute renal failure, a reversible process that needs short term HD or even conservative therapy. One senile patient not scientifically selected for HD, he was a terminal stage of cancer with liver, kidney metastasis and secondary uremia, and he died the 2nd day of starting the HD. Another senile patient with advanced cardiovascular disease and profound arterial hypotension, also badly chosen for HD, unfortunately he died within 72h of his admission. The remaining 78 patients, all were having chronic renal failure in uremic state or what called end stage renal disease (ESRD), diagnosed clinically, and by blood biochemistry. The positive diagnosis was done by clinical findings the most relevant of them were Kaussmaul breathing anemia, hypertension, fluid overloaded, and olguria-anuria, and by blood biochemistry (urea, serum electrolytes, creatinine).

The aetiological diagnosis was supported by history, physical examination and other investigations such as abdominal ultrasound, done in the following days, (as renal biopsy should be avoided in such cases).

All these patients exposed to subclavian catheterization, to facilitate the emergency HD in the following hours, immediate CXR was done to prove the adequate central catheter position, and at the same time to evaluate the heart chambers mainly LVH, and lung congestion.

These patients were haemodialyzed two days weekly, 4h each day session.

On the HD day the patient incorporated to HD ward where he exposed:

• Predialysis weight estimation.
• Predialysis BP measures.
• BP hourly during the 4h haemodialysis.
• Postdialysis BP measures.
• Reweighted again at the end of the dialysis.

The Management of Arterial Hypertension in HD Patients, we applied, Include^6,17,18:

• Haemodialysis HD, and Ultrafiltration UF.
• Antihypertensive medication,(Atenolol, lisinopril, nifedipine, hydrallizine,).
• Achievement of dry weight by intensive and aggressive UF therapy.
• Reduction of interdialytic weight to 1-2 kg (by decrease water intake, and reduce daily NaCl requirement to 2gr).
• Combination of 2,or more of the previous therapeutic modalities.

A follow up of these cases was done to assess the morbid-mortality of the high blood pressure and its complications.

Results and Discussion
Renal failure and dialysis profoundly affect cardiovascular system. In turn abnormalities in cardiovascular system contribute to the symptoms in dialysis patients, that may affect the dialysis regimen¹⁵. Arterial hypertension is considered as a major contributor factor in the frequency and severity of each of the cardiovascular disorders. Prolonged ventricular failure (with poor control of the intravascular volume), and hypertension dramatically affect the presentation and the prognosis of the patients^6,11.

A total number of 78 seriously ill patients admitted as emergency cases of chronic renal failure in ESRD to casualty department at Al Gamhouria teaching hospital, Aden (during 24 months since the inauguration of the haemodialysis center in March 1997) for haemodialysis (HD) therapy. All these patients were centrally catheterized as life-saving procedure to facilitate the effective and rapid HD treatment .The subclavian vein is selected for this purpose.

Younger patients were most commonly involved. Elderly, diabetic, and primary hypertensive patients were not incorporated for HD because of rigid selection criteria, put at this center at the first 2 years. This criterion was adopted because of insufficient facilities.

Table 3 confirms that more than 90% of our uremic patients were hypertensive on arrival (p < 0.001 significant) , this significant rate, play an important rule in the serious long-term prognosis of these patients as stated by various authors ^{11,12,13,14,15}. Hypertension occurs in approximately 80% to 90% of uremic patients before HD ^2,3. Zuccheilli, P. et. al. Confirms this rate and concluded that as the patients progress toward ESRD hypertension became more frequent until nearly all patients are hypertensive before requiring HD⁵.

The majority of our patients were developing mild to moderate hypertension (as shown in table 4). These two grades of high pressure make them more amenable to treatment, regression of LVF, and producing less progressive renal disease ^8,16.

Approximately 90% of the hypertensive cases were volume overloaded with LVH and LVF, (about 75% of the total patients) (table 5 p <0.0001. significant). This rate is higher than what informed by other authors where 50% of their uraemic hypertensive patients were overloaded ¹⁷. The high rate reported by us may partly reflect the delay diagnosis, or that the patients asked medical help too late, in advanced stage of his illness.

This high incidence rate affects negatively the survival of uremic patients. LVH is related strongly to the duration, severity, and uncontrolled hypertension, while the long-term antihypertensive medications has been shown to cause regression of the LVH ^12,15. LVF and LVH is strongly associated with premature death, and arrhythmia ^6,16. Foly, R.N. et. al.¹¹clarified that the relevant causes of LVH in HD patients are, high blood pressure, fluid overload, anemia, and the uremia. It is insisting once more that LV dysfunction is the most important survival determinant than IHD in HD patients ^3,6,18

Our initial approach to control hypertension in the patients entering HD is reduction extracellular volume by Ultrafiltration UF using larger surface area dialyzer, unfortunately only 5% were UF responsive. Patients who have increased interdialytic weight gain and persisting high blood pressure need longer periods of UF and HD^3,4,17, In those patients in whom adequate UF does not control hypertension addition of antihypertensive drugs is necessary, the drugs we commonly prescribed are short acting, avoiding the dosage immediately before dialysis treatment^2,8,9,. Only 7% of the patients we followed showed good response to antihypertensive medication (table 6). UF was not applied in this group because there was no volume overload or weight gain). It looks that both measures (UF and antihypertensive medication) in combination are more effective than simple isolated one, were 26% achieved normal pressure. Atenolol, lisinopril, nifedipine, hydarallazine, are the most common drugs used in our center^2,6,18,.

It is really an interesting data that one third of our patients is not responding even to more intensive antihypertensive therapy, in the other third we were obligated to reduce their daily water ingestion to500-1000ml-day and daily sodium requirement to 2gm, it is just an attempt to decrease the interdialytic weight. Chester,A.L.et.al. Found that 85% of well dialyzed achieved sustained normal blood pressure and become hypotensive with further volume removal³.

The principle causes of this unresponsiveness in our patients may be related to:

• Recurrent interruption of consumes arrival (dialyzers, blood lines, concentrated solutions, needles…) which leads to irregular treatment of high blood pressure by reducing the dialysis days per week and decrease even the hours of each dialysis setting.
• Delay diagnosis, it should be remember that most of the patients with chronic renal failure, came to casualty in emergency state and at the same time in uremic condition ESRD.
• Lack of sufficient experience of the personal staff working in HD center to carry out the great tasks concerning a rapid diagnosis and updated management of hypertension.
• Compliance of the patients to continuo HD therapy, and medication is low, because of economic conditions, inaccessible HD center.

Another dramatic situation is that 31% of our uremic, hypertensive patients died within 2 years of their admission. In other words all those patients dying of ESRD were hypertensive. Again of all the potential risk factor in the development of cardiovascular disease, hypertension may be the most important^{2,3,5,9,15,16,}. Primary hypertension itself is an important cause of progressive renal disease, and when hypertension develops as a result of renal disease is the predominant risk factor for accelerated loss of renal function (viscous circle). Australia and New Zealand dialysis and transplantation (ANZDATA) registry revealed 25% mortality rate within 3 years¹⁸.

So, we think that high blood pressure has a fatal outcome in uremic haemodialyzed patients. Renal hypertension looks to be more likely to progress to an accelerated or As there is an ordered chronological sequences of the following: (A) chronic renal failure (B) hypertension (C) LVH (D) LVF .The prognosis become worst with increasing mortality in progressive order, from A to D.

All patients who died in our wok were complicated with resistant, unresponsive, or badly treated hypertension (reduced HD hours per setting or days per week or not controlling volume) carried the worst outcome. The associated or the appearance of LVF leads to catastrophic fatal prognosis. It is well known that patient undergoing maintenance HD have cardiovascular mortality rate approximately 3 times that of nonuraemic subjects with increase mortality among patients with LVF¹⁵. Cheigh J.S.et al.⁴ And Battistella,P., at. al¹⁹ expressed that ambulatory monitoring of blood pressure BP has showed that BP volume responsive, and hypertension in haemodialyzed patients returned to hypertensive level within 12-24h in the interdialytic period .

We insist once more that adequate control of hypertension is probably not achieved in many haemodialyzed patients in Aden HD center, reason by which we can easily interpretive the disastrous level of mortality among uremic patients undergoing HD.

Conclusion

• Most cases of chronic renal failure attending casualty department in ESRD as emergency patients.
• There was slight male sex predominant.
• The moderate level of blood pressure predominated over the severe and mild hypertension.
• Younger age group was more involved than the others.
• Systemic arterial hypertension is very common cardiovascular manifestation in patients with chronic renal failure in uremic stage (ESRD), approximately 90% of patients incorporated for haemodialysis therapy at Aden HD center (as emergency cases), presented with high blood pressure.
• More than 50% of our hypertensive uremic patients were responsive to combination of fluid removal therapy, antihypertensive drugs, and limitation of water intake.
• One third of these patients remained resistant and unresponsive to all the classical measures adopted for this purpose.
• About 91 % of these hypertensive patients already presented with one of the most serious heart complications of high blood pressure (left ventricular hypertrophy and left ventricular failure LVH, LVF).
• 24 CRF patients undergoing HD (31 %) died within 2 years of their admission, all were hypertensive and hypertension related left ventricle dysfunction.
• Arterial hypertension and LVF were associated with very high mortality rate among patients undergoing haemodialysis, and can be use as prognostic indictor in HD units.
• The 30% of haemodialyzed patients dying within 2 years at HD center in Aden, is considered as catastrophic situation particularly if the international literature reveals "A 10 years mortality increase by 30% in patients with a MAP greater than 99mm\Hg,(European dialysis and transplantation EDTA, registry.), were Australia New Zealand dialysis and transplantation registry ANZDATA clarified that the mortality incidence of about 25 % within 3 years.
• Further approach to uraemic on dialysis patients at HD center Aden is needed to study different influences that may have contribution in the mortality rate rather than the high BP.

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