Prevalence and Hypertension Treatment Schedule in Hemodialysis Patients and Renal Transplant Recipients in 2006 and 2014/2016.

BACKGROUND: Hypertension is often recognized in both hemodialysis patients (HDp) and renal transplant recipients (RTRs). The aim of the study was the evaluation of hypertension prevalence and treatment schedule and the achievement of the control of blood pressure according to the Polish Society of Hypertension, European Society of Hypertension, Joint National Committee, and American College of Cardiology/American Heart Association 2017 recommendations. MATERIALS AND METHODS: Observations were done in 2 distinct periods of time: the year 2006 and the years 2014/2016. In 2006, 56 HDp and 316 RTRs were studied. In 2014/2016, 85 HDp and 818 RTRs were studied. The antihypertensive treatment analysis was based on medical records from visits in RTRs and dialyses in HDp. RESULTS: Cardiovascular diseases were diagnosed in 71.4% (2006) and 65.9% (2016) in HDp; 17.7% (2006) and 21.5% (2014) in RTRs. Diabetes was observed in 39.3% (2006) and 34.1% (2016) in HDp; 16.5% (2006) and 23.2% (2014) in RTRs. The target blood pressure control was achieved in 64.3% (2006) and 49.4% (2016) of HDp and in 61.4% (2006) and 45.7% (2014) of RTRs. Three drugs (28.6% and 33.5% in 2006; 30.6% and 29.1% in 2016/2014) or 2 antihypertensive drugs (19.6% and 26.9% in 2006; 22.4% and 27.1% in 2016/2014) were used in HDp and RTRs, respectively. The majority of HDp and RTRs were treated with ß-blockers followed by calcium channel blockers. CONCLUSIONS: The target blood pressure control was achieved in a low percentage of HDp and RTRs. RTRs required multidrug antihypertensive therapy to control blood pressure more often than HDp.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Renal Transplant Recipients.

BACKGROUND: There is considerable controversy over the benefits of renin-angiotensin system (RAS) blockade in renal transplant recipients (RTRs). The aim of the study was to research the effects of RAS blockade on allograft and patient outcome. METHODS: A retrospective analysis of the effects of RAS blockade on allograft and patient outcome in 53 pairs of RTRs receiving grafts from the same donor was performed. The 106 RTRs (53 pairs), transplanted from 2002 to 2012, were included in the study when 1 patient from the pair used an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for a minimum period of 36 months (RAS[+]) and the second one did not use it (RAS[-]). RESULTS: There were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, reason of end-stage renal disease, mismatches number, total ischemic time, episodes of cytomegalovirus infections, acute rejections, and immunosuppressive treatment. The mean time of observations was 66.28 months ± 24.39 months. RAS inhibitors were given in a mean dose of 23.1% (ACEI) and 27.08% (ARB) of the maximum recommended. The main reasons for the therapy were as follows: hypertension (39.62%), nephroprotection/proteinuria (39.62%), and polyglobulia (28.3%). The composite cardiorenal endpoint was reached by 6 (11.32%) and 7 (13.21%) patients in RAS(+) and RAS(-) group, respectively. There were no differences in changes of creatinine, potassium serum level, or estimated glomerular filtration rate between RAS(+) and RAS(-) patients in the early period after RAS blockade commencement. CONCLUSION: Agents inhibiting the RAS system neither improved nor deteriorated patients and graft survival in RTRs.

Influence of Renin-Angiotensin System Blockers on Graft Function in Retrospective Analysis of Pairs of Renal Transplant Recipients From the Same Donor.

BACKGROUND: Renin-angiotensin system (RAS) blocking agents efficiently control hypertension in renal transplant recipients (RTRs), and reduce proteinuria and post-transplant erythrocytosis. A beneficial effect on the retardation of the long-term decline in renal function has not yet been demonstrated. The aim of the study was to evaluate the effects of RAS blockade on allograft function. METHODS: In order to minimize donor variability and bias, 33 pairs of RTRs receiving grafts from the same donor were included into the retrospective analysis. A total of 66 RTRs were enrolled in which 1 patient from the pair used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a minimum period of 60 months (RAS[+]) and the second one did not use it at all (RAS[-]). RESULTS: There were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, mismatches number, duration of total ischemia, episodes of cytomegalovirus infections, acute rejections, or immunosuppressive treatment. Significantly, more RAS(+) patients presented with diabetes and cardiovascular complications. Among RAS(+) patients, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in 28 (84.84%) and 5 (15.15%) patients in a mean dose of 23.03 ± 16.83% and 30 ± 11.18% of their maximum doses, respectively. There were no significant differences in estimated glomerular filtration rate changes (-0.37 ± 12.68 vs 2.54 ± 20.76 mL/min) and serum creatinine changes (0.05 ± 0.39 vs 0.14 ± 0.79 mg/dL) between RAS(+) and RAS(-) patients during the 60 months follow-up. CONCLUSION: Agents inhibiting the RAS did not significantly affect graft function in RTRs during 60 months of observation.

Management of Renin-Angiotensin-Aldosterone System Blockade in Kidney Transplant Recipients.

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the cornerstone treatment in chronic kidney disease patients. Despite facilitating a reduction in blood pressure and albuminuria, there are insufficient data in kidney transplant recipients (KTRs). They are often administered for hypertension and polycythemia treatment. The aim of this study was to investigate the frequency and route of administration of ACEIs and ARBs and their early clinical effects in the KTR population. In a cross-sectional, retrospective study we analyzed 874 medical records of all KTRs treated in our unit in 2014. A total of 391 KTRs (44.7%) using ARBs or ACEIs were qualified for the study. The primary reasons for renin-angiotensin-aldosterone system antagonist administration were hypertension (59.1%), polycythemia (19.2%), and proteinuria (18.2%). Among the studied KTRs, 86.7% of patients were treated with ACEIs and 12.2% were treated with ARBs. The majority of patients treated with ACEIs and ARBs received these agents in a dose range below 25% and between 25% and 49% of their maximal dose, respectively. Both the mean serum creatinine level and estimated glomerular filtration rate (chronic kidney disease epidemiology collaboration) remained fairly stable and urine protein excretion (g/24 hours) was significantly reduced after 3 months of ACEI and ARB therapy. The serum potassium level increased significantly, while hemoglobin concentration dropped significantly. In KTRs, renin-angiotensin-aldosterone system antagonists were applied mainly due to hypertension, proteinuria, and polycythemia. ACEIs and ARBs were effective in the reduction of proteinuria and hemoglobin, but graft function was stable and the increase of serum potassium was not of clinical significance.

Improvement of Blood Pressure Control in Renal Transplant Recipients-Retrospective Longitudinal Study.

BACKGROUND: Hypertension is a very common complication in renal transplant recipients (RTRs). It has been identified as a potent cardiovascular risk factor associated with impaired patient and graft survival. METHODS: A longitudinal retrospective analysis was performed to evaluate adherence to recommended blood pressure (BP) targets and to estimate the tendency in the management of hypertension from 2001 to 2015. A total of 96 RTRs (55 male, 41 female; overall mean age (2001), 41.66 ± 11.08 years; mean serum creatinine level, 1.45 ± 0.3 mg/dL; 41.2 ± 34.9 months after kidney transplantation) with diagnoses of hypertension and monitored continuously in the unit from 2001 to 2015 were included in the study. RESULTS: The average diastolic BP decreased (P < .01) and the average systolic BP did not change in this period. The target values of BP (ie, <140/90 mm Hg) were accomplished by 45.8% (2001) and 53.1% (2015) of patients. When the target BP was corrected by age (<150/90 mm Hg for people >65 years old) the adherence improved to 57.29% in 2015. The average number of antihypertensive agents used per patient increased significantly (P < .001): 2.03 ± 1.0 (2001) versus 2.69 ± 1.26 (2015). The most commonly used antihypertensive agents were beta-blockers: 69% and 74% in 2001 and 2015, respectively. There was a significant increase in the percentage of RTRs treated with the use of alpha-blockers (P < .01), angiotensin-converting enzyme inhibitors (P < .001), and angiotensin II receptor blockers (P < .05). CONCLUSIONS: The study showed modest improvement of the hypertension control rate from 2001 to 2015 in RTRs. Greater efforts are needed to implement the guidelines, which would further improve patient and graft outcomes.

Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A Pilot Study.

BACKGROUND: The beneficial effect of kidney transplantation in patients requiring continuous renal replacement therapy owing to chronic kidney disease is well known and accepted. Kidney transplantation protects the patient from complications that may develop during chronic dialysis. Unfortunately, there is also evidence that kidney transplant patients are more prone to developing cancer than healthy persons. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after kidney transplantation. METHODS: Adult patients after kidney transplantation, who are under the care of the Outpatient Department of Nephrology in Gdansk, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 45 selected patients (29 men and 16 women) endoscopic examination was performed. Mean age was 57.6 ± 10.1 (range, 35-83) years. RESULTS: Out of ∼940 patients after kidney transplantation, resting under supervision of outpatient department, 181 patients completed the questionnaire and 100 gave a stool sample for testing: 32 results were positive. After analyzing the questionnaires and stool results, 88 patients were qualified for further investigation. The endoscopic examination had been performed so far in 45 patients and revealed gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18, esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel disease in 7, and cancers in 3. CONCLUSIONS: The preliminary results indicate that patients after kidney transplantation have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.

Renal allograft protection with angiotensin II type 1 receptor antagonists.

The renal benefits of agents inhibiting the renin-angiotensin-aldosterone system in renal transplant recipients, i.e. preventing the development of chronic graft nephropathy, are supposed but not finally proven. In a double-blind, placebo-controlled, cross-over study, we evaluated the influence of losartan on surrogate markers of tubular injury, urine excretion of transforming growth factor beta-1 (TGF-beta1) and amino-terminal propeptide of type III procollagen (PIIINP) in 16 patients after transplantation. The patients received randomly either losartan (50-100 mg daily) or the beta-blocker carvedilol (12.5-25 mg) for 8 weeks, allowing a placebo washout between treatments. The target office through blood pressure (BP) was below 130/85 mmHg. The BP did not differ in the treatment periods. Losartan significantly decreased N-acetyl-beta-d-glucosaminidase and alfa-1 microglobulin excretion relative to placebo and carvedilol. Urine excretion of TGF-beta1 and PIIINP was significantly lower after losartan. In conclusion, losartan reduces urine excretion of proteins associated with tubular damage and graft fibrosis.

Natural killer cell activity unaffected by ozonated autohemotherapy in patients with end-stage renal disease on maintenance renal replacement therapy.

Ozonotherapy is a complementary medical approach in the treatment of resistant infections, immune deficiency syndromes, orthopedic pathologies and vascular diseases. The criticism of this method is associated with potentially harmful effects of ozone on cells. The aim of this study was to investigate the influence of ozonated autohemotherapy (O3-AHT) on the cellular response of the immunologic system represented by cytotoxic activity of natural killer cells. 12 hemodialyzed patients (8 M, 4 F) aged 64.8 +/- 7.6 years with peripheral arterial disease as the main reason for the treatment with O3-AHT were examined in a prospective, placebo controlled, single blind study. They received 9 sessions of autohemotherapy without ozone exposure as a placebo-control and subsequent 9 sessions of O3-AHT. The procedures were performed 3 times a week, just before hemodialysis session. Ozone-oxygen gas mixture with ozone concentration of 50 microg/ml produced by ozone generator (ATO3, KrioMetrum, Poland) was used during O3-AHT Natural killer cell activity was measured using lactate dehydrogenase release assay There was no statistical difference between natural killer cell activity (%) at the baseline (16.78 +/- 8.07), after nine sessions of control autohemotherapy (15.98 +/- 6.67), and after nine sessions of O3-AHT (18.26 +/- 8.82). In conclusion, our findings showed that O3-AHT in a dose of 50 mg/mL does not have any significant influence on natural killer cell function in hemodialyzed patients.

Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study.

BACKGROUND: Hemodialyzed patients are particularly exposed to the development of peripheral arterial occlusive disease. Ozonotherapy is used as a therapeutic tool in the treatment of this atherosclerotic complication, but there are still no properly designed studies to show the clinical effectiveness of this approach. The aim of this study was to evaluate the influence of ozonated autohemotherapy on walking ability and the subjective clinical experience of hemodialyzed patients with peripheral arterial disease. METHODS: Ten subjects with intermittent claudication (Fontain II stage) received the cycle of ozonated autohemotherapy with ozone concentration of 50 microg/ml and the cycle of oxygen autohemotherapy as a control in a cross-over, single-blind manner. Pain-free distance and maximal walking distance were measured using a standardized march test on a treadmill. The efficacy of therapy was assessed subjectively by patients on a five-degree scale. RESULTS: Significant prolongation of maximal waking distance after ozonated autohemotherapy was found, as compared to the baseline (by 30.5%) and to the oxygen control (by 22.7%) (p<0.01 and p<0.03). There was also significant increase in pain-free distance after ozonated autohemotherapy, as compared to the baseline (by 71.7%) and to the oxygen control (by 62.8%) (p<0.02 and p<0.03 respectively). In a subjective assessment (questionnaires) 90% of patients reported clinical improvement relative to the baseline after ozonated autohemotherapy as compared to 40% after the oxygen-control treatment (p<0.025). CONCLUSION: We demonstrated that ozonated autohemotherapy might prolong walking ability and attenuate subjective clinical signs of ischemia in patients with peripheral arterial disease treated regularly with hemodialysis.

The influence of ozonated autohemotherapy on oxidative stress in hemodialyzed patients with atherosclerotic ischemia of lower limbs.

Ozonated autohemotherapy is used as a complementary medical approach in the treatment of vascular disorders. One of the greatest problems concerning an application of ozone in medicine is its induction of oxidative stress. The standards of ozonotherapy were elaborated recently making this treatment useful and probably non toxic. The aim of the present study was to investigate the influence of ozonated autohemotherapy on the oxidative stress extent in hemodialyzed patients, known to be particularly exposed to generation and deleterious effects of free radicals. Twelve continuously hemodialyzed subjects with atherosclerotic ischemia of the lower limbs were examined in a prospective, controlled, single blind study. Autohemotherapy with blood exposure to oxygen served as a control. The protein and lipid peroxidation products, the reduced glutathione level in red blood cells and free hemoglobin plasma concentration were measured. The study showed that ozonated autohemotherapy with ozone concentration 50 microg/ml per gram of blood induced a significant decrease in glutathione level after 9 sessions of this procedure. Therapy did not cause either the enhancement of protein and lipid peroxidation, or erythrocytes damage. It seems likely that the antioxidant defense system, part of which is glutathione, neutralizes oxidative properties of ozone in this concentration and protects against oxidative cell damage.

Beneficial clinical effects of ozonated autohemotherapy in chronically dialysed patients with atherosclerotic ischemia of the lower limbs--pilot study.

Ozonated autohemotherapy is a controversial but successful method of treatment, used in particular in European countries. There are many fields in which medical ozone could be of value: treating different infections, immunodeficiency syndromes, neoplasms. Encouraging results have also been achieved in the treatment of atherosclerotic ischemia of the lower limbs. In this preliminary study, the influence of blood ozonation on the intensity of symptoms of ischemia of the lower extremities was analysed among dialysed patients with chronic renal failure. We examined 5 hemodialyzed patients and 7 patients treated with peritoneal dialysis immediately before and after 14 sessions of ozonated autohaemotherapy. Eleven patients (91.6%) reported a subjective decrease in perceived intensity of ischemic pains, or observed prolongation of intermittent claudication distance. During march tests performed on a treadmill, we found significant prolongation of intermittent claudication distance in all examined patients - 65.6% (mean value, p (< or =0.01). Patients treated with peritoneal dialysis achieved much greater improvement than did hemodialyzed patients (165% vs. 42%). We concluded that autohemotherapy with ozone, in a concentration of 34.4 mcg/ml of blood, is safe, easily applied and may be useful In the therapy of atherosclerotic ischemia of lower extremities among dialyzed patients. It could also be a complement to current treatment, especially in cases where the latter has failed.

[Cyclophosphamide pulse therapy in patients with primary glomerulonephritis]. / Leczenie pulsami cyklofosfamidu pacjentów z pierwotnymi glomerulopatiami.

UNLABELLED: Cyclophosphamide is a cytostatic drug, widely used in therapy of secondary glomerulonephritis. Because pulse therapy bears less side effects than oral one we aimed to follow the cyclophosphamide effect on the course of patients with primary glomerulonephritis. We observed 20 pts (7 women and 13 men), mean age 33 +/- 10.0 yrs, age range 18-50 yrs with primary glomerulonephritis and proteinuria more than 3.5 g. 12 patients also had erythro-cyturia. In all pts kidney biopsy was performed, but in one woman the biopsy was not diagnostic. Renal biopsy revealed: FSG in 2 pts, membranous glomerulonephritis in 2 pts, in 9 pts mesangial proliferative changes and in 6--mesangiocapillary lesions. In 5 pts renal failure was observed. Cyclophosphamide was administered i.v. in the dose 0.75 g/m2 b.s., no more than 1.0 g per dose, in renal failure 0.5 g/m2. During the first six months patients received cyclophosphamide every month and then every three months. Before cyclophosphamide pulse therapy all patients were pretreated with steroids, 3 pulses of 1.0 g Methylprednisolone and then oral prednisone in the dose 20 mg/m2 body surface. RESULTS: In 3 patients we obtained remission of proteinuria, in 11 patients decrease of proteinuria but 6 patients didn't answer to the introduced treatment. In whole group of examined patients we obtained the statistically significant decrease of proteinuria from 12.2 +/- 10.5 to 5.3 +/- 5.2 g (p < 0.05) after the treatment. The creatinine clearance did not change in the time of the treatment and any special complications during the treatment were observed. We suggest that cyclophosphamide pulse therapy could be an effective treatment in pts with primary glomerulonephritis. Our results showed that the answer of proposed treatment was independent of the type to the changes found in kidney biopsy.

Hypertensive nephropathy - an increasing clinical problem.

Arterial hypertension-related renal damage is an increasingly common problem recently, because approximately 25% of patients currently treated with dialysis were hypertensive before renal replacement therapy was started. Hypertension is also known as a metabolic disease, while carbohydrate, purine and lipid disturbances are the features of this syndrome. On the other hand, the progression of renal disease depends on the extent of tubulointerstitial injury. For this reason, we undertook a study to evaluate the relationship between excretion of the markers of tubular damage (NAG) and some parameters of carbohydrate, purine and lipid metabolism in untreated essential hypertension. Both healthy volunteers (n = 15) aged 32. 6+/-7.8 and essential hypertensives (n = 25) aged 37.24+/-11.39 underwent the same tests. These tests were performed at 2-day intervals: intravenous glucose tolerance test with 0.5 g/kg b.w. as 40% glucose solution and oral fructose load test with 1.0 g/kg b.w. Area under glucose curve (GA) and serum uric acid post-fructose (PUAA) were calculated. Fasting: insulin, total cholesterol and LDL, triglycerides, free fatty acids (FFA) and urine excretion of NAG, albumin were determined. Glomerular filtration rate was estimated as creatinine clearance. Hypertensives showed statistically higher BMI (p<0.007), NAG (p<0.02), total cholesterol (p<0.01), LDL (p<0.007), FFA (p<0.007), insulin (p<0.01), PGA (p<0.01) and PUAA (p<0.03). NAG excretion correlated positively with WHR (r = 0.40), MAP (r = 0.47) and PUAA (r = 0.47) in hypertensives only. We presume that tubular injury at an early stage of renal damage in patients with essential hypertension could be a part of metabolic syndrome X.