Rafał Donderski

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.

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>3,5g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.

Factors associated with increased pulse wave velocity in peritoneal dialysis patients

Elevated pulse wave velocity (PWV) reflects increased arterial stiffness. Several studies have investigated PWV in peritoneal dialysis (PD) patients, but direct comparisons with healthy controls were not done. The potential influence of peritoneal transport characteristics on arterial stiffness in PD patients was suggested in recent studies. The aims of this study were to compare PWV in PD patients and healthy volunteers, and to investigate factors associated with increased PWV. The carotid-femoral PWV was measured in 28 PD patients and 28 healthy controls, matched for age and gender. A peritoneal equilibration test (PET) was performed in all PD patients. Based on the PET, patients were classified as: high transporters (H) (n=8), high-average (HA) (n=12), low-average (LA) (n=6), and low transporters (L) (n=2). Six of the PD patients were diabetic. PWV was significantly higher in the PD patients than in the controls (9,9±2,4 vs. 8,0±0,9; p=0,0004). In the PD group, PWV was higher in H/HA than in L/LA patients (10,4 ± 2,5 vs. 8,6 ± 1,0; p=0,008), but all the diabetic patients were in the H/HA group. PWV was significantly higher in diabetic than in non-diabetic PD patients (12,8 ± 2,0 vs. 9,1 ± 1,7; p=0,004). In the PD patients, significant positive correlations were found between PWV and: age, pulse pressure, Kt/V, and duration of PD therapy. In conclusion, the carotid-femoral PWV is elevated in peritoneal dialysis patients. Increased PWV in PD patients is associated with age, diabetic status, and longer duration of PD therapy, but not with this type of peritoneal transport.

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.

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.

Prevalence of sleep apnoea in patients with chronic kidney disease (CKD) receiving renal replacement therapy by haemodialysis

Background. Sleep disorders in kidney disease patients occur more frequently than in the general population. Chronic renal disease patients are commonly diagnosed with sleep apnoea syndrome. It occurs in the obstructive, central and mixed form and is of multicausal nature. The aim of the present paper was to assess the frequency of individual types of sleep-related breathing disorders in chronically haemodialysed patients using polysomnography. Material and methods. The study involved stage 5 CKD patients receiving continuous renal replacement therapy by haemodialysis. Results. The obtained results suggest that weight gain between consecutive haemodialysis sessions correlates with more frequent occurrences of disordered breathing events (apnoeas and hypopnoeas) in patients on the night preceding haemodialysis session. Conclusions. Positive linear correlations are observed of systolic and diastolic BP measured before PSG performed on the day before a haemodialysis session with the number of snoring episodes, which might suggest that breathing disorders affect the complex pathogenesis of hypertension in haemodialysed patients.

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

BackgroundFructose 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.MethodsStudies 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).ResultsAbsolute 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.ConclusionsSubjects 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 registrationThe study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526