Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation.

BACKGROUND: Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. METHODS: Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. RESULTS: LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). CONCLUSIONS: The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.

Anemia treatment with darbepoetin alpha in pregnant female with chronic renal failure: report of two cases.

Pregnancy is a rare finding in females with CRF. It is well known that in these cases pregnancy worsens the renal function and accelerates the beginning of dialysis therapy. Pregnancies in uremic females are complicated by a worsening of anemia as well as hypertension, fluid imbalance, electrolyte difficulties, malnutrition, polyhydramnios and preterm labor or sudden intrauterine death. The use of erythropoiesis stimulating agents (ESA) allows a better hematocrit control. Data concerning anemia treatment in pregnants with CRF and data regarding the use of ESA in these patients is scarce. We report two cases of anemia treatment with darbepoetin alpha in pregnant women with CRF in predialysis period and during the hemodialysis therapy. Both patients during the darbepoetin treatment did not require any blood transfusions and at 32nd and 37th weeks of pregnancy delivered healthy infants. The high darbepoetin doses did not cause any side effects, were well tolerated and safe for both gravida and fetus. The effective anemia treatment in pregnants with CRF improves the prognosis for a successful pregnancy.

Diabetic nephropathy and cardiovascular diseases.

Diabetic nephropathy is diagnosed either when persistent increase of urinary albumin excretion rate (UAER) above 30 mg/24h in a patient with diabetes was discovered (early or incipient nephropathy) or when UAER values are persistently elevated above 300 mg/24h (overt or clinical nephropathy). In both situations the additional criteria of presence of diabetic retinopathy and the absence of the evidence of other kidney or renal tract disease should be fulfilled. It was found that the excess of cardiovascular events and mortality occurs already in diabetic patients with persistent microalbuminuria, but is particularly evident in macroalbuminuric diabetic patients and results not only from end-stage renal failure (ESRF) but rather from cardiovascular disease (CVD), the latter mainly in type 2 diabetic patients. Several traditional risk factor for atherosclerosis has been identified in diabetic patients with micro- or macroalbuminuria including elevated blood pressure levels, dyslipidemia and procoagulatory state associated with endothelial dysfunction. Microalbuminuria is currently regarded as a marker of generalized endothelial damage, it reflects transvascular albumin leakage, now recognized as an early event in atherogenesis. Recently the association of microalbuminuria with the marker of chronic inflammation (C-reactive protein) and with increased production of vascular endothelial growth factor (VEGE) was described. Thus, multiple mechanisms are involved in the development and progression of cardiovascular complications both in micro- and macroalbuminuric diabetic patients and all these mechanisms should be regarded as the target for therapeutic intervention.

Can von Willebrand factor, platelet-endothelial cell adhesion molecule-1 and thrombomodulin be used as alternative markers of endothelial cell injury in human glomerulonephritis?

PURPOSE: There is growing evidence that endothelial cells (EC) are active participants of an inflammatory process in glomeruli. MATERIAL AND METHODS: We compared the glomerular expression of three EC-coupled molecules, i.e. platelet-endothelial cell adhesion molecule-1 (PECAM-1 or CD31), von Willebrand factor (vWF) and thrombomodulin (TM) in 60 patients with glomerulonephritis (GN) and five normal kidneys (NK). The alkaline phosphatase anti-alkaline phosphatase method was used to examine the expression of these proteins in the biopsy specimens. RESULTS: In NK, the expression of CD31 and vWF comprised the whole glomerular network. In contrast, the expression of TM was much lower and localized mainly to EC at the vascular pole and adjacent areas. In GN, the glomerular staining for CD31 and vWF was significantly reduced. A fall in the expression of both these EC antigens was more pronounced in proliferative forms of GN (PGN) than in non-proliferative GN (NPGN) (CD31: NPGN vs. PGN, p < 0.02; vWF: NPGN vs. PGN, p < 0.05). In addition, a linear relationship between the expression of CD31 and vWF was found in GN (r = 0.8, p < 0.001). Conversely to CD31 and vWF, a marked increase in glomerular reactivity for TM was observed in all the patients with GN (GN: 2.12 +/- 0.32, NK: 0.95 +/- 0.05, p < 0.02). However, the highest expression of TM was found in membranoproliferative GN and lupus GN. CONCLUSIONS: Our results suggest that CD31 and vWF may be used as markers of glomerular EC loss during GN, whereas TM staining seems to reflect EC activation in response to circulating and/or released in situ procoagulant factors.

Acute and chronic urinary tract infections caused by Chlamydia trachomatis.

Chlamydia trachomatis is one of the causes of acute and chronic urinary tract infections and acute or silent salpingitis. Chronic or recurrent female urinary or genital tract infections with Chlamydia trachomatis have been recognised as a significant factor in the development of acute or chronic renal interstitial inflammation or increased risk of ectopic pregnancy. In most cases Chlamydia trachomatis is sexually transmitted. Moreover, it is one of the most common sexually transmitted pathogens. The current estimate is that in the United States there occur 4.5 million new infections each year. We describe 3 cases of recurrent urinary tract infections due to Chlamydia trachomatis.

Lack of association between Gly460Trp polymorphism of alpha-adducin gene and salt sensitivity of blood pressure in Polish hypertensives.

BACKGROUND: Previous studies have suggested that alpha-adducin (alpha-ADD) polymorphism may identify patients with a salt-sensitive form of hypertension. AIM: To investigate the association between Gly460Trp polymorphism of alpha-ADD and the pattern of blood pressure response to subacute (1 week) salt loading and depletion in young adult thin Polish hypertensives. METHODS: The study group consisted of 44 subjects with salt-sensitive hypertension (SS) and 24 subjects with non-salt-sensitive hypertension (SR). Genomic DNA isolated from peripheral blood leukocytes was amplified by PCR method with primers flanking the polymorphic region. The mismatch near to 3'-end of the upstream primer was introduced to create a Nla III restriction site in Trp 460 allele. In addition, excreted fraction of filtered sodium (FENa), plasma renin activity (PRA) and plasma concentrations of aldosterone (ALDO) were determined on normal, low and high salt diets. RESULTS: FENa on normal or high salt diets were significantly lower in the SS hypertensives as compared with the SR patients. PRA in SS group was also significantly lower as compared with results in SR group, but only on high salt diet. No significant difference was detected in frequencies of genotypes and alleles of alpha-ADD gene between SS and SR subjects. An additional analysis with regard to genotype (Gly/Gly vs. Gly/Trp+Trp/Trp) showed no significant difference in changes of blood pressure as well as in results of laboratory investigations. CONCLUSION: Our results suggest lack of association between Gly460Trp polymorphism of alpha-adducin gene and salt sensitivity of blood pressure in Polish hypertensives.

[Post-transplant nephropathy and arterial hypertension]. / Nadcisnienie tetnicze a przewlekla nefropatia potransplantacyjna.

The introduction of new immunosuppressive regimens results in the significant improvement in the outcome of patients after kidney transplantation. However, about 5 percent of renal transplants are lost every year. Not only immunological (alloantigendependent) but also nonimmunological (alloantigen-independent) factors are involved in late graft loss. Among them, hypertension, hyperlipidemia, proteinuria, genetic predisposition, viral infection and nephrotoxicity of immunosuppressive drugs contribute to the development and to the progression of chronic post-transplant nephropathy. Hypertension can be both the cause and the consequence of chronic allograft failure. Hypertension is frequently observed before transplantation, persists after grafting and increases the risk of chronic allograft nephropathy. Hypercholesterolemia, obesity, atheromatosis, polycythemia, and excessive salt intake are factors contributing in post-transplant hypertension. However, in some cases, hypertension can be transferred with the grafted kidney, as observed in normotensive patients before renal transplantation. In 1 to 12 percent of cases, the cause of post transplant hypertension is the stenosis of the transplant artery. Sometimes the presence of hypertension in renal recipients may result from the recurrence of glomerulonephritis or from the development of glomerulonephritis de novo in the graft. Also immunosuppressive treatment with corticosteroids and cyclosporine A contributes to the increased prevalence of hypertension by 20-30 percent. The development of the graft nephroarteriolosclerosis as a consequence of hypertension accelerates the progression of the post-transplant nephropathy. Adequate control of the arterial pressure (< 140/90) should be achieved in all renal transplant recipients. Reduction in protein and salt intake is important to reduce hyper-filtration and slows the progression of transplant nephropathy. However, pharmacological treatment is usually needed. Angiotensin-converting-enzyme inhibitors, angiotensin II type I receptor antagonists exhibit beneficial hemodynamic effect leading to the reduction of glomerular hypertension and proteinuria. Calcium antagonists besides their systemic antihypertensive effect, can protect renal grafts from vascular and renal toxicity of CyA. Sometimes, combined therapy with these and other antihypertensive drugs and diuretics is necessary.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

[A case of rapidly progressive glomerulonephritis in the course of Wegener's granulomatosis]. / Przypadek gwaltownie postepujacego klebuszkowego zapalenia nerek w przebiegu choroby Wegenera.

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in patients with advanced renal failure requiring dialysis and in such patients clinical remission is possible to occur.

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

[The efficacy of the substitution of carnivit in patients with chronic failure treated with hemodialysis]. / Ocena skutecznosci substytucyjnego stosowania preparatu Carnivit u chorych na przewlekla niewydolnosc nerek leczonych hemodializa.

Low serum concentration of the carnitine is one of the causes of muscle weakness and cardiomyopathy in patients with chronic renal failure treated by hemodialysis. The carnitine facilitate transport of the free fatty acid into the straitened muscle cells where the product of oxidation is energy-ATP. In the present paper we presented the investigation of the influence of L-carnitine substitution on cardiac performance. The results indicate the positive influence of this treatment on metabolic and haemodynamic cardiac parameters. The subjective patients opinion of L-carnitine treatment was also positive.

[Factors causing renal failure in patients with disseminated lupus erythematosus: description of three cases]. / Czynniki wywolujace niewydolnosc nerek u chorych na toczen rumieniowaty ukladowy--opis trzech przypadków.

We describe three cases of patients with systemic lupus erythematosus in which additional infections: mycotic, bacterial and viral deteriorated renal function and patients needed the dialysis treatment. The patients with autoimmunologic disorders are very sensitive for different infections which need rapid diagnosis and intensive treatment.

[Controversial opinions regarding the role of Bcml vitamin D receptor gene polymorphism on parathyroid function, calcium absorption and bone mineral density in persons with normal renal function and patients with chronic renal failure]. / Kontrowersje w opiniach oceniajacych wplyw polimorfizum Bsml genu receptora witaminy D na czynnosc przytarczyc, wchlanianie wapnia i gestosc mineralna kosci u osób z wydolnymi nerkami i chorych na przewlekla niewydolnosc nerek.

This paper summarizes current, but controversial opinions of different authors evaluating the effect of Bsml polymorphism of the vitamin D receptor gene on the parathyroid function, calcium absorption from the digestive tract and bone mineral density (BMD) in persons with normal renal function and in patients with chronic renal failure. On the basis of these data, the recapitulation of the prevailing opinions was undertaken. Contemporary it is admitted, that the persons with bb genotype and normal renal function are at risk for the development of the parathyroid adenomas while in the patients with chronic renal failure the bb genotype may favour parathyroids hyperplasia. It is also believed that bb genotype in the persons with normal renal function facilitates calcium absorption and is associated with greater BMD. Few investigations performed in the patients with chronic renal failure suggest that the BB genotype may partially influence lower BMD in the subgroup of younger patients treated with hemodialysis for a relatively short period. Existing controversies need however further clarification.

[Comparative study of two immunosuppressive treatment methods in patients with focal segmental glomerulosclerosis]. / Porównanie dwóch metod leczenia immunosupresyjnego u chorych na ogniskowa segmentalna sklerotyzacje klebuszków nerkowych.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.