Hypertension in patients on chronic hemodialysis: pathophysiology and treatment

Hippokratia 2004; 8(4):147-150

G Pekovic - Perunicic
Nephrology Dpt, University Hospital Zemun - Belgrdade, Belgrade, Serbia Montenegro

Abstract

The incidence of end-stage renal disease (ESRD) has been doubled over the past 10 years and the leading causes of ESRD are hypertension and diabetes. The prevalence of arterial hypertension among dialysis patients is high and approximately 80-90% of patients are hypertensive by the time chronic renal failure progresses to ESRD. Recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) have published their guidelines for the management of arterial hypertension. Chronic kidney disease (CKD) and ESRD are associated with an increased prevalence of cardiovascular (CV) disease.
The main pathophysiological mechanism of hypertension in dialysis patients is extracellular volume expansion, which is typically sodium sensitive, given the loss of renal function.
All recommendations for management of hypertension in dialysis patients focuses on the CV risk factor in dialysis patients because of hypertension. Hypertension is discussed in the new light of modern CV risk assessment.
The first goal of hypertension treatment in dialysis patients is the achievement of dry body weight and dietary sodium and water restriction. The second goal is pharmacological treatment of hypertension, if it still exists, after the achievement of the first goal.

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Intracerebral hemmorhage in patient with SLE and catastrophic antiphospholipid syndrome

Hippokratia 2004; 8(4):151-154

P Boura, S Papadopoulos, K Tselios, P Skendros, O Dioritou, G Malamis, P Makris, N Lefkos
Division of Clinical Immunology, 2nd Dpt of Medicine, Aristotle University of Thessaloniki, Greece
Intensive Care Unit, Hippokratio General Hospital, Thessaloniki, Greece
Coagulation and Haemostasis Unit, AHEPA Hospital, Thessaloniki, Greece

Abstract

A 31-year-old woman was admitted to the hospital for the investigation of left lower limb thrombophlebitis. History revealed one 1st trimester abortion, arthralgias, photosensitivity and leucopenia during the last months. Laboratory investigation showed positive antinuclear antibodies (ANA) and high titers of anticardiolipin antibodies (ACA). The patient was diagnosed to suffer from SLE and secondary APS. Treatment included steroids, azathioprine, aspirin and low molecular weight heparin (LMWH). Sixty-three days later, she was admitted to the hospital again because of high fever, macroscopic hematuria and dyspnea. Laboratory testing showed anemia and impaired renal function. High-resolution chest CT revealed bilateral multiple peribronchial infiltrates with hemorrhage. MRI angiography of the kidneys revealed left renal vein thrombosis combined with ischemia of the left kidney. Cyclophosphamide and methylprednisolone pulse treatment as well as intravenous immunoglobulins were started immediately. On day 3, the patient developed acute respiratory failure and was transferred to the ICU. Despite intensive immunosuppressive and supportive treatment, she suffered three relapses of alveolar hemorrhage and died on day 40, due to severe intracerebral bleeding. Final diagnosis was catastrophic APS with diffuse alveolar hemorrhage and kidney involvement. The rarity and individuality of the patient, concerning disease aggressiveness and therapeutic interventions is discussed.

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Male dialysis patients are subject to a higher rate of muscle wasting and weakness than female counterparts

Hippokratia 2004; 8(4):155-160

Gk Sakkas, I Stefanidis, V Liakopoulos, KL Johansen
Dpt of Medicine, niversity of California, San Francisco, CA, USA
Division of Nephology, School of Medicine, University of Thessali, Larissa, Greece
Dpt of Medicine, San Francisco VA Medical Center, San Francisco, CA, USA

Abstract

Background. Gender has been shown to have an effect on muscle size, strength and performance. However, in patients on dialysis treatment it is not known whether gender plays a role in the degree of muscle wasting and weakness. Preliminary data have shown that male patients are more affected than female counterparts. We sought to determine whether the muscles of the lower leg are differentially affected in males and females with ESRD.
Material and Methods. Six healthy female controls (F-CON) were compared to 24 female dialysis patients (F-RFP) and 13 male controls (M-CON) compared to 27 male dialysis patients for measurements in muscle cross sectional area (CSA) and composition by MRI, isometric leg muscle strength, body composition by DEXA, physical activity by a 3D-accelerometry and physical performance using functional tests. The data were normalized for baseline differences between males and females by dividing the variables for each subject by the mean values of the sex-specific control group. ANOVA was performed to detect statistical differences.
Results. Muscle size in M-RPF group was reduced 13% more than in F-RFP group (p=0.01). Muscle strength was also reduced in M-RFP 5% more than the F-RFP group (p=0.01). Intramuscular fat content was similar in all groups. On the other hand, F-RFP group had 20% more reduction in gait speed than M-RFP group (p=0.01). A similar reduction in physical activity levels, lean body mass and total body fat was found in both dialysis groups. Testosterone concentration was highly correlated with muscle size in M-RFP group (R=0.554, p=0.001).
Conclusions. Male patients have a greater reduction in muscle size and strength than female dialysis patients while female patients have a greater reduction in gait speed. Hormonal changes may be a reason for those differences.

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Immunotherapy with an oral bacterial extract for urinary tract infections

Hippokratia 2004; 8(4):161-165

M Malliara
General Hopsital of Katerini, Katerini, Greece

Abstract

Background. This study has made to demonstrate efficacy and safety of oral bacterial extracts in reducing the number of urinary tract infection episodes.
Patients and methods: In 20 patients (group A), we gave 1 capsule per day of bacterial extract during 3 months with their conventional antibiotics. All the patients having had more than 2 urinary tract infections during the last 6 months and having actually an acute infection with dysuria, fever and bacteruria. In 10 patients (group B) with the same criteria we did not gave bacterial extract but only antibiotics and we used them as the control group. The duration of the study was 9 months. Women were 60%, chronic renal failure and nephrolithiasis persisted in 20%. Gram (-) bacteria revealed in 80%.
Results: The first 3 months 54 % of the patients from group A had none recurrence. After 6 months from the end of receiving bacterial extract in group A: 37 % had 1 episode and 67 % in the control group (p < 0.05). The intensity and duration of symptoms were diminished in A group in comparison with the control group. Adverse reactions like diarrhoea and headache revealed in 4 % not so serious to discontinue the medicine. All the patients finished this rotocol. We conclude that the purified bacterial extracts diminish the intensity and the recurrences of urinary tract infections. They seem to be safe and effective without serious sides effects.

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Dependance of dispersion of cardiac calcifications on some biochemical markers in hemodialysis patients

Hippokratia 2004; 8(4):166-169

D Yonova, M Geogiev, S Antonov, Z Kirijakov
Clinic of Nephrology, Medical University Hospital "Alexandrovsca", Sofia, Bulgaria

Abstract

Background: The damage of arteries and heart structures are a major contributory factor to the high cardiovascular morbidity and mortality of patients with chronic renal failure on dialysis. The aim of the study was to find some risk factors for development of cardiac valve calcifications and their relations to myocardial function in patients on hemodialysis treatment.
Material and methods: Conventional M-mode and B-mode echocardiography (Echo) and Pulse-doppler were made, accounting myocardial function and aorta valve calcifications (Ca-Ao), mitral valve calcifications (Ca-M) and total valve calcifications score (Cardiac Ca) of 37 patient with mean age 54.7±14.5 years and mean duration of hemodialysis treatment 82.05±27.35 months. Arterial blood pressure (ABP) and pulse rate were also registered. Tests of serum levels of Ca++, P, alkaline phosphatase (AP), parathormone (PTH), C -reactive protein (CRP), homocysteine and in 20 patients - fetuin-A and serum Mg were correlated to some myocardial functions (ejection fraction-EF; endsystolic stress - ESS; VpE / VpA), muscle mass index (MMI) and valve calcifications rate.
Results: Some significant correlations were found as follows: Ca++ / Cardiac Ca r:0.46, p < 0.01, PTH / Cardiac Ca r: 0.43, p < 0.01, EF / ESS r: 0.81, p < 0.01, EF / Cardiac Ca r: -0.38, p < 0.05, CRP / EF r: -0.4, p < 0.01, MMI / MAP r: 0.52, p < 0.01, VpE / VpA: Cardiac Ca r: -0.38, p < 0.05, Age / Cardiac Ca r: 0.4, p < 0.01, Dur.HD / Cardiac Ca r: 0.28, p < 0.05, PTH / EF r: -0.22, n.s., Fetuin A / PTH r : -0.33 p < 0.05, Fetuin A / CRP r: -0.43, p < 0.001, Fetuin A / Cardiac Ca r: -0.71, p < 0.001
Conclusion: The results prove the negative influence of increased myocardial burden (ESS, ABP) on the left ventricular function and on MMI. Close relations of disturbed mineral metabolism, PTH, inflammatory status (CRP), fetuin A, age and duration of HD with the rate of valve calcifications show that cardiac calcium deposits have multifactorial origin. The study also suggests that valve calcifications are involved in the complex of risk factors, causing damage of the valve structures and left ventricular dysfunction in HD patients.

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Comparative study of oxidative stress in peritoneal dialysis and hemodialysis patients

Hippokratia 2004; 8(4):170-172

D Yonova, , Trendafilov, V Papazov, I Stanchen, R Zidarov, S Antonov
Clinic of Nephrology, Medican University Hospital "Alexandrovska", Sofia, Bulgaria

Abstract
Background: Two general types of extrarenal depuration are used in patients with terminal uremia - peritoneal dialysis (CAPD) and hemodialysis (HD). All uremic patients are exposed to oxidative stress, due to uremia "per se" and some artificial materials are suspected as well, but not surely proved.
Material and methods: The study compares some plasma markers of oxidative stress in 22 patients on CAPD (1st group) ( 12 males and 10 females) and 22 HD patients (2nd group), (12 males and 10 females) more than 24 months on dialysis: MDA and oxidized LDL (ELISA) and, of antioxidant activity: enzymatic - glutathione peroxidase (GPx) (enzymatic assay): and non-enzymatic factors: vitamin E and vitamin C (HPLC). All patients -non-diabetic and without peritonitis - were tested for above mentioned biochemical markers (before HD for the 2nd group).
Results: The existence of oxidative stress was proved to be in both groups. CAPD patients had lower levels of markers of oxidative stress (NS) and significantly higher antioxidant activity for vitamin E and GPx (p < 0.01 and p < 0.01 respectively) compared to patients in HD group. The measured values for 1st / 2nd group were: MDA 6.01±0.33 ??mol / l versus 6.21±0.23 ??mol / l (p: NS); oxidized LDL 350 ±230 mU / ml versus 366±252 mU / ml (p: NS); GPx 18.8± 5.8 ??moll / Hb versus 14.8±4.7 ??mol / Hb (p < 0.01) and vitamin E 24.7±4.4 ??mol / 1 versus 20.8±5.3 ??mol / l (p < 0.01); vitamin C 52.12±26.2 ??mol / l versus 50.2±25.6 ??mol / 1 (p: NS).
Conclusion The findings suggest that uremia is playing the main role in oxidative damages even in dialysis faze of chronic renal failure, but CAPD seems to be slightly more bio -compatible than conventional HD, probably because of the greater number of artificial materials used in the latter. In conclusion dialysis patients more or less need some kind of antioxidant treatment in both dialysis procedures - CAPD or HD despite CAPD has some advantages.

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Renal osteodystrophy in peritoneal dialysis and hemodialysis patients: what is the difference?

Hippokratia 2004; 8(4):173-175

D Yonova, P Dukova
Clinic of Nephrology, Medical University Hospital "Alexandrovska", Sofia, Bulgaria

Abstract

Background: Two general types of renal osteodystrophy(ROD) are recognized in patients on dialysis, excluding the third, mixed one - high bone turnover ROD (HBT) and low bone turnover ROD (LBT). When the "golden standard" - bone biopsy - can not be used, a complex of serum markers quite successfully replace it: intact parathormone (iPTH), bone alkaline phosphatase (BAP), osteocalcin (OC), reflecting bone formation rate and ?�-crosslaps (BC) - pyridinoline and dioxypiridinoline (DYP) - reflecting bone re-absorption.
Material and methods: We compared the prevalence of HBT or LBT by measuring the above mentioned biochemical parameters in 20 pts on peritoneal dialysis (CAPD) (10 males and 10 females) and 20 hemodialysis (HD) pts, (10 males and 10 females) who were for more than 30 months on dialysis and they were non-diabetics.
Results: The CAPD / HD groups showed 143±55 ng / ml versus 923±451 ng / ml (p < 0.001) iPTH levels, 102±77 u / 1 versus 345±256 u / 1 (p < 0.01) HP levels, 12.3±5.4 ng / ml versus 21.5±7.9 ng / ml (p < 0.05) OC levels, 142±14.1 ng / ml versus 221±66 ng / ml (p < 0.05) PICP levels and 15.8±6.8 ng / ml versus 53.5±24.3 ng / ml (p < -.01) DYP levels.
Conclusion: These findings suggest that there is a significantly higher HBT in pts on HD compared to pts on CAPD and point out the importance of investigation and follow up of each dialysis patient, as HBT and LBT are not definitely the privilege of any kind of extra-renal purification method. The existence of a different LBT subtype in HD pts and lack of it in PD pts may be due to the influence of the artificial HD materials on the production of cytokines, potent to increase bone re-absorption.

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Hypercalcemia, hypercalciuria and nephrocalcinocis associated with high vitamin D intake in an infant

Hippokratia 2004; 8(4):176-178

DB Kuzmanovska, EM Shahpazova, SJ Grujovska, MJ Kocova, E Sukareva
Nephrology Dpt, Gastroenterology Dpt, Endocrinology Dpt, University Pediatric Clinic, Skopje, F.Y.R.O.M.

Abstract

We report an eight month - old female infant who presented with hypercalcemia, failure to thrive, polyuria and dehydration following excess vitamin D supplementation: the first eight months of life. At birth, she weighed 3000 gr and at admission to the hospital her weight was 6700 gr. She presented serum calcium concentration 3.6 mmol/1, calciuria 14 mg/kg and the renal ultrasound revealed nephrocalcinosis.
The intact PTH was low (< 3 pg/ml). Although 25(OH) vitamin D3 plasma level was not measured, after rehydration and after evaluation of the prevailing pathogenic mechanism, prednisone was given for treatment of hypercalcemia. The beneficial response, with no recurrence of hypercalcemia / hypercalciuria after discontinuation of prednisone and introduction regular milk formula, provides strong evidence that hypercalcemia, hypercalciuria and nephrocalcinosis were due to vitamin D intoxication.
To diagnose vitamin D intoxication, one must consider it in the differential diagnosis and obtain a history of vitamin D intake in infants with hypercalcemia / hypercalciuria and failure to thrive of obscure origin.

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Magnesium deficiency in type 2 diabetes

Hippokratia 2004; 8(4):179-181

Z Rasic - Milutinovic, G Perunicic - Pekovic, S Pljexa, A Dangic, V Libek, Lj Bokan, M Cancovic - Kadijevic

Abstract

Background. Controversial reports are available regarding the effect of magnesium (Mg) on glycaemic control and lipids profile in diabetic patients. The present study was designed to compare serum Mg levels of type 2 diabetic patients with those of non-diabetic controls and to assess the relationship between serum Mg levels and metabolic parameters of type 2 diabetic patients and healthy control subjects.
Patients and Methods: The study was randomized, cross -sectional and 90 healthy blood donors and 38 patients with Type 2 diabetes were recruited. Serum glucose, insuline, total cholesterol, triglycerides, total Mg++ and Ca++ were measured. Weight, height and blood pressure were recorded. BMI and IR were calculated.
Results: Plasma glucose level, and calculated IR HOMA were significantly higher in diabetic subjects, as we expected (glucose 3.98±0.10 mmol / l vs. 6.60±0.70 mmol / l, p: 0.04, IR 3.28±0.21 mU / l vs. 6.39±0.15 mU / l, p: 0.01). Plasma lipids, Total cholesterol (Total ch) and triglycerides (5.42± 0.98 mmol / l vs. 7.30±2.20 mmol / l, p: 0.04, 1.78± 1.12 mmol / 1 vs. 3.5±1.87 mmol / l, p: 0.01) were also significantly higher in diabetic patients. Serum Mg was lower significantly in diabetic subjects (0.83±0.03 mmol / l vs. 0.77±0.09 mmol p: 0.04). In healthy subjects serum Mg level negatively correlated with body mass index (BMI) (r: -0.316, p < 0.01), systolic blood pressure (SBP) (r: -0.326, p < 0.01), and diastolic blood pressure (DBP) (r: -0.346, p < 0.01). In diabetic group serum Mg level negatively correlated with serum insulin (r: -0.233, p: 0.05), IR HOMA (r: -0.280, p: 0.04), Total ch (r: -0.331, p: 0.02), triglycerides (r: -0.378, p < 0.01) and with SBP (r: -0.380, p < 0.01) and DBP (r: -0.272, p: 0.04).
Conclusion: The results of the present study have shown lower serum Mg level in type 2 diabetic patients and demonstrated that almost all components of metabolic syndrome in diabetic patients were associated with serum Mg level.

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Soft tissue calcifications in patients on dialysis treatment

Hippokratia 2004; 8(4):188-190

D Yonova, M Georgiev, S Antonov, Z Kirijakov
Dialysis Clinic, Medical University Hospital "Alexandrovska", Sofia, Bulgaria

Abstract

Background: Patients with end stage renal failure on dialysis treatment may develop several types of soft tissue calcification, including visceral, periarticular and vascular calcifications due to a number of known and unknown factors. The aim of the study was to evaluate the dispersion of vascular and periarticular soft tissue calcifications of a random group of haemodialysis (HDT) patients and their relation to parathyroid hormone (PTH) and some other biochemical markers.
Material and methods: Four middle-range arteries a.a. carotis communis sinistra et dextra and a.a. femoralis sinistra et dextra were investigated by B-mode echography; 4 typical for calcium deposits periarticular regions of the body were checked by x-ray and visible skin calcifications were registered in 40 patients (on HDT more than 3 months) for evaluation of calcification rate, comparing them with some biochemical parameters: PTH, alcaline phosphatase (AP), Ca, Ca++, P and C-reactive protein (CRP).
Results: The study revealed a high percentage (95 %) of vascular calcifications (VC), and a low percentage of periarticular and skin calcifications (3.3 %). A significant correlation was found between PTH / AP (r: 0.7, p < 0.001), PTH / VC (r: 0.51, p < 0.001), PTH / Ca++ (r: 0.40, p < 0.01) and PTH / CRP (r: 0.39, p < 0.01) as well as between CRP / VC (r: 0.38, p < 0.01).
Conclusion: The study suggests an influence of secondary hyperparathyroidism and existing inflammatory status on vascular calcifications in dialysis patients but no relation of both factors to periarticular and skin calcium deposits, which would require a different way of therapy.

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Improvement in uremic symptoms after increasing daily dialysatte volume in anuric peritoneal dialysis patients

Hippokratia 2004; 8(4);182-187

V Liakopoulos, M Krishnam, I Stefanidis, DG Oreopoulos

Abstract

Background. Patients on peritoneal dialysis (PD) can develop uremic symptoms as their residual renal function declines and they finally become anuric. In this retrospective study, we assessed the effect of increasing the dose of dialysis in anuric patients who developed uremic symptoms.
Materials and Methods. We evaluated retrospectively the effect of increasing the dose of dialysis on the prevalence of uremic symptoms in 44 anuric PD patients in whom the dose of dialysis was increased during the last five years. We also reviewed the charts of 12 patients with no increase in their dialysis dose, despite the onset of anuria. We recorded data for fatigue, anorexia, insomnia, pruritus and nausea, urine and peritoneal clearances, serum creatinine, BUN, PO4, Hb, EPO dose, blood pressure and weight for a period of 6 months before and 6 months after the change in the PD prescription.
Results. Of the 44 patients (mean age 52±16, with 43 %males), 37 were on continuous ambulatory peritoneal dialysis (CAPD) and 7 on continuous cycler peritoneal dialysis (CCPD). Twenty three percent were diabetics; mean duration of PD before the change in dialysis dose was 27.8±18 months. Daily dialysate volume was increased an average of 2.2 L in CAPD and 4.3 L in APD patients. Peritoneal Kt / V and weekly creatinine clearance increased from 1.91±0.04 to 2.44 ±0.08 and from 49.8±1.2 to 61.5±2.1 L/week respectively. The prevalence of fatigue decreased from 80 % to 38 %, anorexia from 50 % to 20 %, insomnia from 45 % to 11 %, pruritus from 34 % to 9 % and nausea from 11 % to 4 %. All these changes were statistically significant. On the other hand, we observed a slight trend towards an increase, but certainly no decrease, in the prevalence of uremic symptoms in the 12 patients, whose dialysis dose remained unchanged. Of these patients with a mean age of 60±16 years (58 % males and 58 % diabetics) 9 were on CAPD. Their peritoneal Kt/V was 2.04±0.25 and their weekly creatinine clearance 54.7±7.8 L. Before the onset of anuria, the prevalence of fatigue was 50 %, anorexia 25 %, insomnia 33 %, pruritus 33 % and nausea 0 %. After six months of established anuria these figures became 83 %, 25 %, 25 %, 33 % and 17 % respectively.
Conclusion: After a little over two years on PD most anuric patients develop uremic symptoms. Fatigue is the most common symptom followed by anorexia. An increase in the dialysis dose leads to a decrease in the prevalence of all the symptoms. Such an increase in prescription should be considered if PD patients become symptomatic.

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