Assessment of Peritoneal Membrane Arteriolar Structure in Conjunction with Traditional Cardiovascular System Evaluation in Chronic Kidney Disease (CKD) Stage 5 Patients.

BACKGROUND/AIMS: Cardiovascular complications are responsible for increased mortality and morbidity in chronic kidney disease (CKD) patients. Functional and structural changes of peritoneal membrane are reported in CKD patients both on conservative treatment and on renal replacement therapy (RRT). The aim of the study was to assess the structure of peritoneal membrane small arteries (precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients before initiation of peritoneal dialysis (PD) and evaluate its relationship with heart and large arteries abnormalities and with selected biochemical parameters. METHODS: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic (n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane samples were taken during Tenckhoff catheter insertion. Histopathological evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio was performed in each patients. Echocardiography, intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH), hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P), transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each participant. RESULTS: There were no statistically significant differences in peritoneal membrane arteriolar indices - wall thickness (WT) and L/V ratio between investigated groups. There was statistically significant higher PWV value in diabetic patients. There were no statistically significant differences in echocardiographic indices, IMT, laboratory data in analyzed groups. There were some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP (R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age (R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in diabetic group. CONCLUSION: Peritoneal membrane arteriolar damage seems to be an integrated part of cardiovascular system damage in CKD stage 5 patients.

The fructose tolerance test in patients with chronic kidney disease and metabolic syndrome in comparison to healthy controls.

BACKGROUND: Fructose acutely raises serum uric acid in normal subjects, but the effect in subjects with metabolic syndrome or subjects with chronic kidney disease is unknown. The aim of the study was to evaluate changes in serum uric acid during the fructose tolerance test in patients with chronic kidney disease, metabolic syndrome with comparison to healthy controls. METHODS: Studies were performed in 36 subjects with obesity (body mass index >30) and metabolic syndrome, 14 patients with stage 3 chronic kidney disease, and 25 healthy volunteers. The fructose tolerance test was performed in each patient. The change in serum uric acid during the fructose challenge was correlated with baseline ambulatory blood pressure, serum uric acid, metabolic, and inflammatory markers, and target organ injury including carotid intima media thickness and renal resistive index (determined by Doppler). RESULTS: Absolute serum uric acid values were highest in the chronic kidney disease group, followed by the metabolic syndrome and then healthy controls. Similar increases in serum uric acid in response to the fructose tolerance test was observed in all three groups, but the greatest percent rise was observed in healthy controls compared to the other two groups. No significant association was shown between the relative rise in uric acid and clinical or inflammatory parameters associated with kidney disease (albuminuria, eGFR) or metabolic syndrome. CONCLUSIONS: Subjects with chronic kidney disease and metabolic syndrome have higher absolute uric acid values following a fructose tolerance test, but show a relatively smaller percent increase in serum uric acid. Changes in serum uric acid during the fructose tolerance test did not correlate with changes in metabolic parameters, inflammatory mediators or with target organ injury. These studies suggest that acute changes in serum uric acid in response to fructose do not predict the metabolic phenotype or presence of inflammatory mediators in subjects with obesity, metabolic syndrome or chronic kidney disease. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526.

Analysis of relative expression level of VEGF ( vascular endothelial growth factor ), HIF-1α ( hypoxia inducible factor 1α ) and CTGF ( connective tissue growth factor ) genes in chronic glomerulonephritis (CGN) patients.

BACKGROUND/AIMS: Analysis of gene expression in renal tissue is considered to be a diagnostic tool predicting the clinical course of glomerulonephritis. The present study quantified the relative transcript levels of VEGF, CTGF and HIF-1α in renal tissue to establish their relationship with some clinical variables in patients suffering from chronic glomerulonephritis (CGN). METHODS: 28 patients (6F and 22M, mean age 51.2±15.0) with CGN were enrolled. Type of CNG recognized by kidney biopsy (histopatological evaluation) was as follows: minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts, lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology was taken as control. Mean clinical follow-up of patients was 12 months after biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of biopsy and then in 6 months intervals. Real-time PCR was used to determine relative gene expression. The housekeeping gene GAPDH was used as normalization control. RESULTS: At the time of the biopsy relative expression of 3 analyzed genes was diminished in comparison to control. There were statistically significant differences in VEGF gene relative expression level in patients which varied according to eGFR and tendency in patients which varied according to DPE. HIF-alfa and CTGF gene showed only a tendency. CONCLUSIONS: Overexpression of the VEGF gene in subjects with DPE>3,5 g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.

"Sweet" Hydrothorax in a Peritoneal Dialysis Patient. A Case Report and Review of the Literature on Novel Diagnostic and Therapeutical Approaches.

"Sweet" hydrothorax is a rare complication of peritoneal dialysis (PD). It is characterized by the presence of peritoneal fluid in the pleural cavity. We describe the case of a 41-year-old woman who developed this complication three days after starting continuous ambulatory peritoneal dialysis (CAPD). We present the current diagnostic approach and treatment of this rare complication.

The enhanced renin-angiotensin-aldosteron system pharmacological blockade--which is the best?.

BACKGROUND/AIMS: Pharmacological inhibition of renin-angiotensin-aldosteron system (RAAS) may reduce proteinuria and the rate of chronic kidney disease progression. The aim was to compare the effects on albuminuria of the therapy with either: (i) telmisartan 80 mg and aliskiren 300 mg, (ii) telmisartan 80 mg and eplerenone 50 mg, (iii) telmisartan 160 mg as monotherapy. DESIGN AND PATIENTS: Randomized, double-center, double-blind, cross-over, three treatments-three periods of 8 weeks each study. 18 patients with non-diabetic proteinuric CKD stage 1-3 completed the protocol. RESULTS: There was significant difference in albuminuria between studied therapies (ANOVA; p<0.01). The combination therapy with telmisartan plus aliskiren decreased albuminuria more effectively than the treatment with telmisartan plus eplerenone and monotherapy with telmisartan 160 mg OD [376 mg/g creatinine (286-686) vs. 707 (502-1204) vs. 525 (318-763); post-hoc p<0.01 and p<0.05, respectively]. CONCLUSIONS: The study demonstrated that the combination therapy with angiotensin receptor blocker (ARB) and renin inhibitor was more effective in albuminuria lowering than the concomitant usage of ARB and mineralocorticoid receptor antagonist as well as than ARB in doses two-fold higher than usually used in treatment of hypertension in patients with non-diabetic CKD and that this higher antiproteinuric efficacy was independent on changes in blood pressure.

Hepatorenal Syndrome and Other Post-Liver Transplantation Complications: Case Studies and Literature Review.

Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.

Analysis of profibrogenic microRNAs (miRNAs) expression in urine and serum of chronic kidney disease (CKD) stage 1-4 patients and their relationship with proteinuria and kidney function.

PURPOSE: Besides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage. METHODS: Assessment of 45 chronic kidney disease (CKD) patients stage 1-4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD-EPI equation: eGFR < 60 ml/min, eGFR > 60 ml/min) and different daily protein excretion (DPE): (DPE < 3.5 g; DPE > 3.5 g). RESULTS: Increased relative expression of hsa-miR-29-5p, hsa-miR-21-5p, and hsa-miR-196a-5p and decreased expression of hsa-miR-155-5p, hsa-miR-214-5p, hsa-miR-200a-5p, and hsa-miR-93-5p was demonstrated in urine of analyzed CKD patients. In subpopulation of chronic glomerulonephritis (CGN) patients, there was higher level of expression in urine of hsa-miR-155-5p, hsa-miR 214-3p, hsa-miR-93-5p, and hsa-miR-196a-5p in CGN with DPE < 3.5 g. CGN patients with eGFR < 60 ml/min showed higher expression level of miRNAs such as hsa-miR-214-3p, hsa-miR-29-5p, hsa-miR-93-5p, and hsa-miR-196-5p in urine. There was increase in hsa-miR 155-5p, hsa-miR-214-3p, and hsa-miR-200a-5p serum expression level in CKD population and reduction of hsa-miR-29a-5p, hsa-miR-21-5p, and hsa-miR-93-5p expression. Increased level of expression of hsa-miR-155-5p; hsa-miR-214-3p, hsa-miR-200a-5p, and hsa-miR-29-5p was found in CGN patients with eGFR > 60 ml/min. CONCLUSION: Increased relative expression of profibrogenic miRNAs in urine or serum of CKD patients with eGFR > 60 ml/min and DPE < 3.5 g may indicate higher degree of fibrosis at early CKD stages.

Abnormal diurnal blood pressure profile and hypertension-mediated organ damage in nondiabetic chronic kidney disease G1-G3b patients.

OBJECTIVE: Chronic kidney disease (CKD) is associated with high cardiovascular risk. Prevalence of hypertension and hypertension-mediated organ damage (HMOD) increases with CKD progression. Nocturnal blood pressure (BP) is a strong predictor of cardiovascular complications. This cross-sectional study investigated the link between the diurnal BP profile and HMOD in nondiabetic CKD G1-G3b patients. METHODS: We investigated 109 CKD patients and 41 apparently healthy persons as controls. All subjects underwent 24-ambulatory blood pressure monitoring (ABPM), echocardiography with left ventricular mass index (LVMI) calculation and pulse wave velocity (PWV) measurement. RESULTS: Hypertension was present in 84% of CKD patients. SBP-24 and DBP-24, SBP-day and DBP-day did not differ between CKD and controls. Significant differences were found in SBP-night and DBP-night. The nondipping BP profile (SBP-night/SBP-day ratio ≥0.9) was found in 62% of CKD patients and 32% of controls (P < 0.005). Nocturnal hypertension was found in 56% of CKD patients. LVMI was higher in CKD compared to controls, higher in nondipping than dipping CKD patients, and higher in patients with nocturnal hypertension than without nocturnal hypertension. Abnormal left ventricular geometry was found in 72% nondipping and 43% dipping CKD patients. PWV was higher in CKD than in controls, in patients with nocturnal hypertension than without nocturnal hypertension but did not differ between CKD nondippers and dippers. CONCLUSION: The nondipping BP profile and nocturnal hypertension are associated with HMOD in G1-G3b CKD patients. Hence, there is a need for more extensive use of ABPM for individual risk assessment and personalization of antihypertensive treatment in CKD patients.

Achromobacter xylosoxidans Relapsing Peritonitis and Streptococcus suis Peritonitis in Peritoneal Dialysis Patients: A Report of Two Cases.

Peritonitis is considered to be the most common complication of peritoneal dialysis (PD). It is usually caused by Gram positive Staphylococcus epidermidis. Achromobacter xylosoxidans (A. xylosoxidans) and Streptococcus suis (S. suis) are rare pathogens, but there is emerging evidence that they may be also responsible for PD related peritonitis. We described 2 cases of rare peritonitis treated in our center. In our opinion this is the first described case of PD related peritonitis caused by Streptococcus suis.

[Role of vitamin D3 in arterial blood pressure control]. / Rola witaminy D3 w patogenezie nadcisnienia tetniczego.

The basic function of vitamin D3 in human body is to maintain the calcium-phosphate homeostasis. Its metabolic function is mediated by the nuclear VDR receptor. The existance of vitamin D3 receptors outside tissues and organs which take part in calcium-phosphate metabolism has resulted in not treating it as an anti rickets agent only. Lower arterial blood pressure observed in people living in sunny areas and decrease of arterial blood pressure values after exposure to UVB radiation could confirm the relationship between vitamin D3 and hypertension. Perhaps through its influence on calcium-phosphate metabolism, RAA system, immune system, control of endocrine glands and endothelium function the vitamin D3 contributes to lowering arterial blood pressure and lessening the risk of cardiovascular disease.

Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients.

BACKGROUND: High aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment. METHODS: Twenty-two patients on PD were assigned to spironolactone treatment in dose of 50 mg daily during 12 months. Fifteen PD patients were assigned to control group. Echocardiographic indices, PVW, SBP, DBP (mean values from ABPM) and biochemical parameters such as: aldosterone, osteopontin, IL-6, selectin-P, TGF-ß, PTH, MMP-2 were performed at the beginning and after 12 months in spironolactone and control group. RESULTS: There were no statistically significant differences in echocardiographic indices, PWV, BP (ABPM readings) and biochemical markers: MMP-2, serum aldosterone, TGF-ß, IL-6, selectin-P, PTH level after 12 months of spironolactone treatment. There was statistically significant rise in osteopontin level after 12 months of spironolactone treatment. Episodes of life-threatening hyperkalemia were not reported. CONCLUSIONS: Aldosterone antagonists use in PD patients seems to be safe. Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients. Further studies are required to determine relationship between mineralocorticoid receptor blockade and mineral-bone disturbances in PD patients.

[Endothelial dysfunction in peritoneal dialysis patients and its relationship to nutrition]. / Zaburzenia funkcji sródblonka u chorych dializowanych otrzewnowo i ich zwiazek ze stanem odkywienia.

Endothelial dysfunction (ED) in peritoneal dialysis patients plays pivotal role in progression of atherosclerosis and hemostasis disturbances. Malnutrition is one of the most important complication of PD. Both ED and malnutrition cause higher rate of cardiovascular events in these patients. 32 PD patients were analyzed. Endothelial function was assessed by measurements of serum level of vWF:Ag; t-Pa:Ag; TM:Ag. Nutritional status assessment included: body mass index-BMI, MAMC measurements; and serum albumin, total protein, prealbumin, transferrin, cholesterol, insulin, insulin like growth factor-1 (IGF-1). There were higher levels of vWF:Ag but lower of t-PA:Ag and TM:Ag after 12 month of observation. Serum levels of prealbumin, insulin, cholesterol were stable, but there were lower levels of albumin, IGF-1, and higher of transferrin at the end of the follow up. There were no differences in anthropometric indices during the follow up. We found statistically significant linear correlations: t-Pa:Ag vs prealbumin; t-Pa:Ag vs cholesterol; TM:Ag vs albumin. In the course of 12 months observation of peritoneal dialysis patients we found deterioration of endothelial function, expressed by evaluated endothelial antigens. Some correlations found in our study might express close relationship between endothelial function markers and nutritional status.

Safety of enhanced renin-angiotensin-aldosterone system inhibition with aliskiren in nondiabetic patients with chronic kidney disease.

INTRODUCTION: Various methods of combination renin-angiotensin-aldosterone system blockade help achieve more potent antiproteinuric effects, but may be associated with higher risk of side effects. Therapies involving direct renin inhibitor, aliskiren, may promote renal fibrosis by stimulating (pro)renin receptor due to increased renin levels. OBJECTIVES: The aim of the study was to compare the effects of combination treatment with angiotensin receptor blockers, telmisartan (80 mg/d) and aliskiren (300 mg/d) with those of combination treatment with 80 mg/d telmisartan and mineralocorticoid receptor blocker (50 mg/d eplerenone) and telmisartan (160 mg/d) alone on the urinary excretion of transforming growth factor ß1 (TGF­ß1), renal function, and serum potassium levels. PATIENTS AND METHODS: A randomized open-label controlled cross-over study was performed in 18 white patients (7 women and 11 men; mean age, 42.4 ±1.9 years) with proteinuric nondiabetic chronic kidney disease and estimated glomerular filtration rate of 85.2 ±4.6 ml/min. RESULTS: The urinary excretion of TGF­ß1 was stable despite a significant increase in plasma renin levels after treatment with telmisartan and aliskiren. There were no differences in renal function and serum potassium levels between the compared treatments. Moreover, there were no episodes of hypotension or acute renal impairment. CONCLUSIONS: Combination therapy with telmisartan and aliskiren may be safe in young nondiabetic patients with normal renal function at low vascular risk. This treatment may be an alternative for a subset of patients in whom standard RAA system blockade is ineffective.

Comparison of arterial stiffness in end­stage renal disease patients treated with peritoneal dialysis or hemodialysis.

INTRODUCTION: Dialysis patients presents increased arterial stiffness. Results of available studies comparing arterial stiffness in peritoneal dialysis (PD) patients vs hemodialysis (HD) patients are inconsistent. OBJECTIVES: The aim of the study was to compare pulse wave velocity (PWV) in PD and HD patients and to compare value of measured PWV (PWV(M)) with theoretical value of this parameter (PWV(T)) calculated using formula developed by Blacher et al. From the equation it is apparent that PWV increases by 0.8 m/s for each decade of life. PATIENTS AND METHODS: Carotid-femoral PWV(M) was measured in 35 PD and 26 HD patients, using Complior device. In all patients PWV(T) was also calculated. RESULTS: The study groups did not differ significantly with respect to age, gender, and prevalence of diabetes. The value of PWV(M) (PD:12.1 ± 3.3 vs HD:12.0 ± 3.0 m/s) and PWV(T) (PD:10.0 ± 1.4 vs HD:9.9 ± 1.2 m/s) did not differ significantly between PD and HD. PWV(M) was significantly higher than PWVT in both, PD and HD patients. Diastolic blood pressure and mean arterial pressure was higher in PD patients, but systolic blood pressure and pulse pressure did not differ significantly. In PD patients a higher number of antihypertensive medications was used (3 ± 1 vs 2 ± 1;p<0.05). CONCLUSIONS: Arterial stiffness is equally high in peritoneal dialysis patients and in hemodialysis patients. Measured value of PWV in both, PD and HD patients, is significantly higher when compared with theoretical value of PWV. This finding may reflect accelerated arterial aging in patients on dialysis.

Acquired hemophilia: a case report.

Acquired hemophilia is a severe bleeding diathesis that affects both males and females. It is caused by suddenly appearing autoantibodies that interfere with coagulation factor VIII activity. This disorder is characterized by spontaneous and post-traumatic subcutaneous bleeds and massive mucosal hemorrhages. We report in the current article a case of acute renal failure and bleeding from the urinary tract caused by idiopathic acquired hemophilia in a 54-year-old woman. Hemostatic tests indicated prolonged activated partial thromboplastin time (APTT) to 107.8 sec (norm 26-36 sec), normal value of the prothrombin index which was 82% (norm 70-130%), increased fibrinogen concentration to 583 mg/dl (normal value 200-400 mg/dl), the bleeding time was 5 min and 20 s (norm < 10 min) and the platelet count was 366 x 10(9)/l (norm 130-400 x10(9)/l). The autoantibody against factor VIII in a titer of 121 Bethesda Units/ml (BU/ml) and decreased factor VIII activity to 2% (norm 50-150%) with normal plasma concentration of factor IX. Activated (FEIBA, Baxter) and nonactivated prothrombin complex concentrates (factor IX concentrate) have been used in the treatment of bleeding episode. Immunosuppressive treatment with the combination of oral prednisone 60 mg/24h and cyclophosphamide 150 mg/24h was administered in order to remove the factor VIII inhibitor. Reduction of the factor VIII inhibitor titer to 38 BU/ml and increase of factor VIII activity to 4% was initially achieved. This treatment has been continued for two years and led to normalization of hemostatic parameters (APTT 26 sec, factor VIII activity 108%) which means a total removal of factor VIII inhibitor.

Lipid Peroxidation, Advanced Glycation end Products and Antioxidant Status in Patients on Dialysis.

Oxidative stress increases the risk of cardiovascular disease in patients on chronic dialysis. In this study, we examined markers of oxidative stress and antioxidant status in haemodialysis (HD) patients in order to find out their relationship to the dialysis treatment. Study included 25 patients on long-term haemodialysis (HD) and 30 control subjects. Levels of malonyldialdehyde+4-hydroxyalkenes (MDA+4-HNE), advanced glycation end products (AGEs) and superoxide dismutase (Cu/ZnSOD) were assayed in plasma or serum. Mean plasma level of MDA+4-HNE was 2-fold higher and AGEs 4-fold higher in HD patients, comparing to control subjects. Also Cu/ZnSOD were significantly elevated in dialysis patients. Positive correlation between AGEs as well as Cu/ZnSOD concentration and duration of HD treatment (r=0,68, p<0,007; r=0,53, p<0,006) was found. Significantly increased oxidative stress may accelerate atherosclerotic changes and cardiovascular complications in haemodialysis patients but seems to be, at least in part, counteracted by enhanced antioxidant capacity.