The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats.

Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.

Effect of Immunosuppressive Therapy on Proteinogram in Rats.

BACKGROUND It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. RESULTS Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. CONCLUSIONS (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively.

Wegener's granulomatosis and pyoderma gangrenosum--rare causes of facial ulcerations.

BACKGROUND: Pyoderma gangrenosum (PG) is caused by immune system dysfunction, and particularly improper functioning of neutrophils. At least half of all PG patients also suffer from autoimmunological diseases, one of which is Wegener granulomatosis (WG). The purpose of this article was to compare cases of patients with WG and PG in terms of their clinical course, histopathology, and applied treatment. In both, histopathological features are not fully distinct. Data from microbiological and immunological evaluation and clinical presentation are required to establish the diagnosis. We also present the case of a patient with WG and deep facial skin lesions not responding to standard treatment. METHODS: Systematic review of the literature in PubMed using the search terms "Wegener granulomatosis AND Pyoderma gangrenosum" and case report. RESULTS: The finding of 22 reports in the literature (PubMed) suggests that it is a rare phenomenon. This study revealed a similar rate of comorbidity of WG and PG in both genders and an increased incidence of both diseases after the age of 50. Among skin lesions there was a dominance of ulceration, most often deep and painful, covering a large area with the presence of advanced necrosis and destruction of the surrounding tissue. The most common location proved to be the cervical-cephalic area. The most popular treatment included steroids with cyclophosphamide. DISCUSSION: The rarity of the coexistence of these two diseases results in a lack of effective therapy. In such cases sulfone derivatives are still effective and provide an alternative to standard immunosuppression methods. Hyperbaric therapy and plasmapheresis can also play an important complementary role.

[Old age--neither sour nor bitter]. / Starosc--ani kwasna, ani gorzka.

The development of medicine involves prolongation of human life. In many cases, however, chronic diseases, quite common in the elderly, make the quality of life very poor. We put the question: why we--the doctors--are not able to cope with the problem and whether the pharmacological treatment actually helps? A common medical practice is the use of proton pump inhibitors for various, often nonspecific disorders of the gastrointestinal tract. Statistics point to the overuse of the drugs from this group, also in the elderly. Despite the belief in the safety of such proceedings, proton pump inhibitors may pose a significant threat to older patients contributing to the symptoms worsening, and significantly affecting the mechanisms of acid-base balance. Inhibition of gastric acid secretion in the stomach is not a golden receipt in the case of dyspeptic symptoms, especially in people with the elderly. In many of them achlorhydria or hipochlorhydria is diagnosed. In others, such treatment, may not bring an expected relief in symptoms, while contributing to disturbances of acid-base balance, and--indirectly--have an adverse effect on renal function. We suggest moderation in the use of proton pump inhibitors to bring patients to a real, and not quasi wellness.

Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus.

New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney transplant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C>T) using PCR-based assays. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P=0.056), and an association of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR)=2.45, P=0.023) was observed. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR=2.35, P=0.026). Patients' higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk factors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in relation to PTDM risk. However, the application of SNP-63 (rs5030952:C>T) as a marker of PTDM should be verified by further independent studies.

Platelets arachidonic acid metabolism in patients with essential hypertension.

Arachidonic acid's (AA) metabolites, eicosanoids, exert a tremendous influence on circulatory and vascular homeostasis, and in humans are generated by many organs and cell types. In this study we wanted to verify whether platelets AA metabolism play a significant role in pathogenesis of essential hypertension (EH). Participants were divided into the study (EH) and the control group. Plasma and urine concentrations of isoprostanes (8-iPF(2alpha)-III) and thromboxane B(2) (TxB(2)) were determined using the ELISA method. The levels of 5- and 12-hydroxyeicosatetraenoic (HETE) acids, generated by platelets, were analysed using RP-HPLC. In a suspension of not stimulated and AA-stimulated platelets TxB(2) level was statistically lower in the study than in the control group (p < 0.0001 and 0.001 respectively). The concentration of 12-HETE was significantly elevated in EH patients compared to the control group; however, only in the non-stimulated conditions (p < 0.05). Plasma and urine F2-isoprostanes levels were significantly higher in hypertensive individuals than in the control group (p < 0.00002 and p < 0.01 respectively). Moreover, EH patients excreted more TxB(2) in urine than normotensive individuals (p < 0.05). Our results highlight the mutual connections between the platelets AA metabolism and indicate its possible role in the pathogenesis of arterial hypertension. Moreover, we hypothesize that platelets AA metabolism may exert a pro-atherosclerotic effect. Finally, we suggest the use of (5-HETE+12-HETE)/TxB(2) parameter in further studies.

Urobiome: In Sickness and in Health.

The human microbiome has been proven to contribute to the human condition, both in health and in disease. The metagenomic approach based on next-generation sequencing has challenged the dogma of urine sterility. The human urobiome consists of bacteria and eukaryotic viruses as well as bacteriophages, which potentially represent the key factor. There have been several significant findings with respect to the urobiome in the context of urological disorders. Still, the research on the urobiome in chronic kidney disease and kidney transplantation remains underrepresented, as does research on the role of the virome in the urinary microbiota. In this review, we present recent findings on the urobiome with a particular emphasis on chronic kidney disease and post-kidney transplantation status. Challenges and opportunities arising from the research on the human urobiome will also be discussed.

Biocompatibility of synthetic ultraviolet radiation cross-linked polymers - Subcutaneous implantation study.

Photo-cross-linked polymers have attracted a lot of attention in the biomedical field. The main benefits of these materials are related to the fact that they are most of the time viscous liquids or pastes that adapt a custom and fixed shape on demand of the user. Present study deals specifically with the biological response upon subcutaneous implantation of four different materials in rabbits. In the study 20 rabbits were divided into four groups (each five rabbits): Groups 1-3 were implanted with tested new obtained by us macromonomers (P1838-DMA; P1838-UR; PDEGA-UR - respectively), while group 4 (control) was implanted with the mesh (PLA) routinely used for surgical treatment of a hernia. The new compounds were polarized earlier using ultraviolet radiation to obtain cross-linked networks. The polymers in the form of discs were then implanted subcutaneously in dorsal region of rabbits. After 28 days polymers were explanted and examined. Microscopic observation evaluated: thickness of the connective tissue capsule around the discs, cells of inflammatory response, disc surface erosion, spectroscopic analysis. The examined materials cause no chronic inflammation, abscesses or tissue necrosis, and the biological response is similar to observed in control group. Therefore, new synthetic materials could be considered as biocompatible and safe. Materials undergo slow degradation of ester bonds and surface erosion and degradation products could be eliminated probably by phagocytosis. On the basis on the afore mentioned knowledge, we formulated hypothesis, that the new polymers are well tolerated by the adjacent tissues. The aim of the following study was to examine reaction of the tissue on new types of prepolymerized material implanted subcutaneously. The obtained results suggest, that the new UV cross-linked polymers do not affect negatively on the connective tissue that is in the contact with the implants. Furthermore, the used materials are in the liquid form, thus they could be easily performed in in minimally invasive laparoscopic treatment of abdominal hernias. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1889-1897, 2019.

Influence of angiotensin I-converting enzyme polymorphism on development of post-transplant erythrocytosis in renal graft recipients.

BACKGROUND: Post-transplant erythrocytosis (PTE) is estimated at 5-20%. Angiotensin II generated by angiotensin I-converting enzyme (ACE) stimulates erythropoiesis. The highest activity of ACE is observed in DD genotype. The question arises if ACE gene polymorphism influences PTE. METHODS: One-year prospective study included 89 kidney recipients (28 women and 61 men). RESULTS: Thirty-four (38%) recipients proved to be DD genotype, 36 (40%) ID, and 19 (22%) II genotype. Absolute PTE [hematocrit level (HCT) >50% and RBC > 5.5 mln/mm(3)] was found in 14 (19%) patients. PTE developed 6-12 months after kidney Tx. There were no significant differences in genotype distribution between patients with and without PTE. ANOVA showed that the most significant predictor of PTE development was the time since kidney Tx (p < 0.0001). Analysis of logistic regression showed that male sex was the most important factor in PTE development 12 months after kidney Tx (OR = 13.6: 95% CI 1.2-150.9, p < 0.05). D allele increased the PTE risk (OR = 3.3 for each allele: 95% CI 1.1-10.4, p < 0.05), the use of angiotensin-converting enzyme inhibitors (ACEI) decreased the PTE risk (OR = 0.15: 95% CI 0.03-0.85, p < 0.05). In patients with DD genotype, there was a correlation between hemoglobin, RBC and HCT concentration, 12 months after Tx and panel of reactive antibody value before Tx (Rs = +0.43, p < 0.05). CONCLUSIONS: Male sex and D allele presence increase the risk of PTE development, especially in highly immunized patients. The use of ACEI decreases the risk of PTE development.

Influence of glucose in the dialysate on the activity of erythrocyte-glutathione-peroxidase and blood selenium concentration in hemodialyzed patients.

BACKGROUND: The aim of the study was to show the influence of glucose in the dialysate on the intensity of oxidative stress, activity of glutathione peroxidase (GSHPx) and concentration of selenium in patients undergoing regular hemodialysis. METHODS: The study was comprised of 85 patients hemodialyzed with dialysate containing glucose [HD-g(+)] or not containing glucose [HD-g(-)], patients with chronic renal failure on conservative treatment and control group. The concentrations of the products of reaction with thiobarbituric acid (TBARS), concentration of selenium in erythrocytes and plasma, concentration of copper in erythrocytes and the activity of GSHPx were determined. RESULTS: GSHPx had significantly higher activity in HD-g(-) group before HD than in control group. In HD-g(+) group before hemodialysis, the activity of GSHPx was significantly lower than in the control group. After HD, the activity showed a statistically significant increase. In both hemodialyzed groups, selenium concentration before hemodialysis both in plasma and erythrocytes was significantly lower, compared to control group. In the group of patients with CRF on conservative treatment, selenium concentration in RBC was significantly higher, compared to concentrations obtained in other groups except for control group. The increase of copper concentration in erythrocytes was accompanied by the increase of oxidative stress and increase of TBARS concentration. The opposite relationship was observed for selenium-its concentration was inversely correlated to copper concentration. CONCLUSIONS: In both groups of hemodialyzed patients, hemodialysis caused the increase of GSHPx in erythrocyte activity and increase of plasma and erythrocyte selenium concentration.

Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

OBJECTIVES: Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. MATERIALS AND METHODS: We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. RESULTS: No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. CONCLUSIONS: The results of this study indicate that various factors associated with allograft donors may influence graft function.

Birth defects in juvenile Wistar rats after exposure to immunosuppressive drugs during pregnancy.

INTRODUCTION: Immunosuppressive drugs and their active metabolites can cross the placental barrier and enter fetal circulation. The adverse effects on the fetus include chromosomal aberrations, structural malformations, organ-specific toxicity and intrauterine growth retardation. The aim of our study was to investigate the impact of "safe" and "contraindicated" immunosuppressive drugs on birth defects in juvenile Wistar rats after exposure of pregnant female rats to these drugs. MATERIAL AND METHODS: The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. RESULTS: Treatment with mycophenolate mofetil and everolimus turned out to be toxic. We have noticed a significantly reduced number of live births in all pregnant rats exposed to these drugs in combination with calcineurin inhibitors and prednisone. Malformations and histological changes of fetal organs were confirmed after mycophenolate mofetil exposure during pregnancy. CONCLUSIONS: Mycophenolate mofetil turned out to be more toxic when used with tacrolimus than with cyclosporin (delivery of live offspring was possible only in the latter group). Everolimus in combination with cyclosporin effectively suppressed the fetal maturation in utero, but did not contribute to the development of malformations.

Autosomal dominant polycystic kidney disease reduces the risk of diabetes mellitus.

BACKGROUND: Patients with autosomal dominant polycystic kidney disease (ADPKD) are at greater risk of new-onset diabetes after transplantation as compared with other renal graft recipients. METHODS: We mailed questionnaires to 459 ADPKD patients retrieved from the Polish Registry of ADPKD. We analyzed data from 291 respondents and 271 siblings with a known status of ADPKD and diabetes. RESULTS: The prevalence of transplant-unrelated diabetes was significantly higher in siblings without ADPKD (8.2%) than in respondents (1.7%; p = 0.0028) and their ADPKD siblings (2.0%; p = 0.023). Univariate logistic regression demonstrated that the prevalence odds ratio (POR) for transplant-unrelated diabetes in the pooled ADPKD group vs. siblings without ADPKD was 0.21 (95% CI: 0.08-0.54, p = 0.0013). Multivariate regression accounting for age and gender disclosed an even smaller POR for diabetes (0.18) in ADPKD patients (95% CI: 0.07-0.47, p = 0.00049). Age was a significant risk factor for diabetes (POR 1.05, 95% CI: 1.01-1.09 per year of life; p = 0.025) and gender was without effect. The prevalence of diabetes in females and males with vs. without ADPKD was similar (1.6% vs. 8.3%, p = 0.0091 for females; 2.2% vs. 8.0%, p = 0.069 for males). Age and gender were not inter-related. In the group of siblings without ADPKD diabetes was associated with higher age (62.2 +/- 15.6 vs. 47.0 +/- 16.3 years, p = 0.0053). CONCLUSIONS: Our findings demonstrate lower prevalence of transplant-unrelated diabetes among ADPKD patients. We hypothesize that metabolic disturbances in polycystic kidneys suppress the synthesis of endogenous glucose and reduce renal breakdown of insulin.

GNB3 C825T and ACE I/D polymorphisms on the sodium-proton exchanger and the prevalence of essential hypertension in males.

BACKGROUND: The aim of the study was to verify the hypothesis if the interaction between the G protein beta3 subunit (GNB3) C825T polymorphism and ACE I/D polymorphism could lead to the disclosure of increased activity of sodium-proton exchanger and hypertension. METHODS: The study included 44 male patients, median age: 40 years. Patients were divided into two groups: 26 patients with essential hypertension (EH), and 18 subjects in the normotensive group (C). RESULTS: CT + TT genotypes of GNB3 predominated in patients with hypertension (65%) compared to normotensive patients (12%) (p <0.01). No significant differences were observed in the frequency of ACE gene polymorphisms between the examined groups. Significantly higher activity of erythrocyte NHE in patients with EH was observed: median 8.83 (interquartile range 4.27) mmol/l RBC/h, compared to C: median 6.18 (2.80) mmol/l RBC/h, p <0.001. Multiple logistic regression analysis showed that the presence of the T allele increased the risk of hypertension 16-fold (p <0.01) and higher erythrocyte NHE activity 2-fold per each unit of activity (p <0.01). DD genotype of ACE polymorphism did not increase the risk of hypertension. No significant interaction of the influence of GNB3 T allele and ACE DD genotype on the risk of hypertension was observed. In multiple linear regression analysis, none of the examined genotypes and their interactions influenced NHE activity. CONCLUSIONS: The presence of the T allele of GNB3 polymorphism and increased activity of erythrocyte NHE independently of ACE genotype increase the risk of hypertension.

The Role of Klotho Protein in Chronic Kidney Disease: Studies in Animals and Humans.

The identification of Klotho gene was a major discovery as the gene encodes a protein regulating multiple functions. A defect in Klotho gene expression in mice results in a phenotype of premature aging including shortened life span, growth retardation, hypogonadism, skin and muscle atrophies, vascular calcification, cognition impairment, motor neuron degeneration and others. This phenotype is associated with phosphate balance disorders and underlines the major function of Klotho in mineral metabolism. As another 2 related paralogs were discovered (beta-Klotho, which is involved in bile acid and energy metabolism, and gamma-Klotho, with a yet to be defined function), this led to the revised naming of Klotho as alpha-Klotho. Two forms of alpha-Klotho protein have been reported: a membrane-bound and a soluble one. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate co-receptor for the FGF-23 phosphatonin in distal tubules. The soluble form of Klotho seems to function as a humoral factor and regulates glycoproteins on the cell surface including ion channels and growth factors. There is data suggesting that soluble Klotho exerts phosphaturic effects independently of FGF-23. Circulating soluble Klotho is produced either by proteolytic cleavage of the extracellular domain of the transmembrane form by two membrane-anchored proteases (ADAM10 and ADAM17) or by alternative mRNA splicing. In animal models Klotho has been shown to exert pleiotropic actions, including cytoprotection, anti-oxidation, anti-apoptosis, protection of vasculature, promotion of angiogenesis and vascularization, inhibition of fibrogenesis and preservation of stem cells. The exact diagnostic and therapeutic role of Klotho in humans is not fully known yet. The article presents the role of Klotho in physiology and different stages of chronic kidney disease (CKD).

Effects of an immunosuppressive treatment on the rat prostate.

The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins.

Does Immunosuppressive Therapy Affect Markers of Kidney Damage?

BACKGROUND: Markers currently used to detect kidney damage are effective in both early (KIM-1, NGAL) and late (MCP-1, MMP, TIMP) stages of renal tubular damage, indicating the progression of chronic kidney disease. Immunosuppressive drugs may damage the transplanted organ through their direct toxic effects and by contributing to the development of chronic fibrosis and tubular atrophy. The aim of this study was to determine if immunosuppressive drugs per se affect the concentration of kidney damage markers, by using concentrations and doses of immunosuppressive within therapeutic, not toxic, levels in rat blood. MATERIAL AND METHODS: The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporin A, rapamycin, and prednisone). The rats were treated with a 3-drug protocol for 6 months. No drugs were administered to the control group. The blood samples were collected to determine the concentration of kidney damage markers by using enzyme-linked immunosorbent assay (ELISA). RESULTS: 1. In the groups receiving regimens based on cyclosporin A (CyA), significantly higher concentrations of KIM-1 in plasma was observed compared to cases not treated with drugs. 2. The use of tacrolimus was associated with increased concentrations of MCP-1 in plasma and rapamycin was associated with decreased concentrations of MCP-1 in plasma. 3. Rapamycin induces an unfavorable, profibrotic imbalance between metalloproteinase-9 and its inhibitor, TIMP-1. CONCLUSIONS: Commonly used immunosuppressive drugs influence the concentration of blood markers of kidney damage. This fact should be taken into account when analyzing the association between the concentration of these markers and pathological processes occurring in the transplanted kidney.

Renal handling of uric acid in patients with type 1 diabetes in relation to glycemic control.

BACKGROUND: The aim of the study was to compare the renal handling of uric acid (UA) in 16 patients with type 1 diabetes without renal failure (age 34.8 +/- 13.3 years) and in 15 healthy subjects (age 34.9 +/- 12.6 years). METHODS: Creatinine clearance (Cr-Cl), clearance of uric acid (UA-Cl), fractional excretion of uric acid (UA-FE), and 24-h urinary UA excretion (UA-U) were determined. Glycemic control was assessed using fasting glucose, glycated hemoglobin and fructosamine tests. RESULTS: Patients with diabetes had significantly (p < 0.0001) lower serum UA concentrations compared to control group (2.8 +/- 0.7 vs. 5.7 +/- 0.8 mg/dl), and higher urinary UA excretion (813 +/- 107 vs. 423 +/- 40 mg/day), UA clearance (21.9 +/- 7.1 vs. 5.2 +/- 0.9 mL/min) and fractional UA excretion (17.1 +/- 5.5 vs. 4.8 +/- 1.3%), with higher creatinine clearance (129 +/- 16 vs. 111 +/- 12 mL/min, p < 0.005). In patients with diabetes there was a strong negative correlation between serum UA concentration and UA 24-h excretion (R = -0.79; p < 0.001). Fractional UA excretion correlated with fasting glycemia and HbA1c (R = +0.51 and +0.53; p < 0.05). CONCLUSIONS: In type 1 diabetes there is significant UA renal clearance increase, which is higher with poor glycemic control. It leads to hypouricemia despite an approximately twofold UA excretion increase and therefore despite increased UA synthesis.

Plasma prekallikrein as a risk factor for diabetic retinopathy.

BACKGROUND: The aim of the study was to verify the hypothesis that in diabetes there is an increased activation of coagulation system leading in consequence to diabetic retinopathy. METHODS: Thirty three healthy subjects (controls, 16 males and 17 females) and 35 patients with diabetes type 1 (15 males and 20 females) were examined. We monitored plasma prekallikrein (PPK), glycemia, fructosamine, glycosylated hemoglobin, activated partial thromboplastin time (PTT), INR, fibrinolysis in euglobulins time (FET), level of antithrombin III (AT III), fibrinogen (Fb) and fibrinogen degradation products (FDP). RESULTS: In diabetic patients without retinopathy, PKK concentration was 16% higher (p <0.005), in patients with background retinopathy 33% higher (p <0.001), and in patients with proliferative retinopathy PKK concentration was 50% higher (p <0.001) than in controls. In the subgroup of patients with proliferative retinopathy PTT was significantly shorter (p <0.001), and FET was significantly longer (p <0.001) than in control. In patients with diabetes higher FDP concentrations were found than in controls (p <0.05). Significant correlations were found between PPK and fructosamine levels in all diabetic patients (R(S)=+0.57 p <0.001), in diabetic patients without retinopathy (R(S)=+0.61, p <0.05), and in diabetic patients with retinopathy (R(S)=+0.62, p <0.005). We found negative correlation between PPK concentration and PTT (R(S)=-0.43, p <0.001) and positive correlation between PPK concentration and FET (R(S)=+0.59, p <0.00001) in the entire study group. CONCLUSIONS: The occurrence of diabetic retinopathy is connected with higher levels of plasma prekallikrein.