Cardiovascular Involvement in Patients with Autosomal Dominant Polycystic Kidney Disease: A Review.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease with a prevalence of 1:400 to 1:1,000 in Caucasians. It is caused by mutations in the PKD1 gene located on chromosome 16p13.3 (in about 85% cases) as well as in the PKD2 gene on chromosome 4q13-23. In the Polish population, the disease is associated with PKD1 mutations in 84% of the ADPKD-affected families. PKD1 and PKD2 genes encode the proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The presence of kidney cysts is a characteristic feature in the ADPKD patients. But in the ADPKD patients, cardiovascular abnormalities, such as hypertension (HT) with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, higher left ventricular mass (LVM), intracranial (ICAN) and extracranial aneurysms, and cardiac valve defects, are significantly more common than in the general population. SUMMARY: According to the literature data, both higher LVM and vascular dysfunction already occur in children and young adults with normal renal function and without HT. Moreover, biventricular diastolic dysfunction, endothelial dysfunction, increased carotid intima-media thickness, and impaired coronary flow velocity reserve are present even in young patients with ADPKD who have normal HT and well-preserved renal function. In patients with ADPKD, hypertension has some specific features; in the youngest age group of children, the prevalence of hypertension is greater if their parents suffer from hypertension; in normotensive young ADPKD-diagnosed individuals, ambulant SBP and DBP values were significantly higher than in age- and gender-matched controls; hypertension appears at least 10 years earlier than spontaneous HT in general population. In adults, HT is often diagnosed before any substantial reduction in the GFR, and a lower nocturnal dip in BP in comparison to hypertensives in the general population. PKD1 and PKD2 gene products (PC1 and PC2 proteins) have been shown to assemble at the plasma membrane and to regulate calcium (Ca2+) entry. A defect in Ca2+ binding mediated by mutations in polycystin proteins is a hypothetical factor contributing to left ventricular mass increase. Altered intracellular Ca2+ handling contributes importantly to impaired contractility associated with heart failure. Impairment of intracellular Ca2+ homeostasis and mitochondrial function has been implicated in the development of LVH. KEY MESSAGES: It can be assumed that the cause of LVH in ADPKD patients is the natural course of this disease with developing HT and deteriorating kidney function, which may be influenced by the presence of PKD1- and PKD2-mutated gene products: PC1 and PC2 proteins.

The Role of Endothelins, IL-18, and NGAL in Kidney Hypothermic Machine Perfusion.

Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and ET-3), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) during the reperfusion of human kidneys grafted from brain dead donors and later transplanted. The study group (n = 44) was analyzed according to the method of kidney storage: Group 1 underwent hypothermic machine perfusion (HMP) in the LifePort perfusion pump (n = 22), and Group 2 underwent static cold storage (SCS) (n = 22). The analysis of kidney function was performed daily during the first seven days after transplantation. The kidneys in Group 1 were characterized by higher absolute concentrations of ET-1, IL-18, and NGAL, as well as a lower concentration of ET-2 (p = 0.017) and ET-3. The relative increase of ET-1 (p = 0.033), ET-2, and ET-3 during reperfusion was lower in this group, while the relative decrease of NGAL was higher. Group 1 was also characterized by significant decrease of IL-18 (p = 0.026) and a tendency for better kidney function based on the higher total diuresis, higher glomerular filtration rate (GFR), higher potassium level, lower serum creatinine, and lower urea concentration during the seven-day postoperative observation period. The long-term beneficial impact of hypothermic machine perfusion on the outcome of transplanted kidneys may rely on the early modified proceedings and intensity of ischemia-reperfusion injury reflected by the dynamics of the concentrations of examined biomarkers.

Activity of Cathepsin B in Serum of Patients after Kidney Transplantation Depends on Glucocorticosteroids Treatment.

BACKGROUND: Kidney diseases are characterized by deterioration of the function of this organ, often leading to irreversible failure, where transplantation is the only alternative to permanent dialysis. Proteolytic enzymes, including cathepsins B, cleave the peptide bond by hydrolysis reaction. They are also involved in pathological processes such as carcinogenesis and inflammatory processes. The aim of this study was to determine the activity of cathepsin B in the serum of patients after kidney transplantation and to assess the correlation with glucocorticosteroids treatment. MATERIAL AND METHODS: In the study, blood samples of 100 renal transplant recipients were used. The subjects were divided into groups according to the time elapsed since transplantation and the use of steroids in the current and primary treatment. Enzyme activity was measured by spectrofluorometric technique. RESULTS: The study showed significant correlations of cathepsin B with the time since renal transplantation (p<0.05) and steroid used in the primary and current treatment. Steroid treatment is associated with a decrease of the activity of cathepsin B in serum. CONCLUSIONS: The obtained results show decreasing activity of cathepsin B with longer time elapsed since transplantation. We have shown that steroids decrease activity of cathepsin B after renal transplantation. A significant increase in cathepsin B activity is observed mainly in cancer and atherosclerosis. Decreased activity of cathepsin B is probably due to the stabilizing action of steroids on the lysosomal membrane. The impact of steroid therapy for patients with these diseases appears to be significant.

Evaluation of renal graft function based on standard mathematical formulas.

BACKGROUND: Creatinine is a standard marker for estimation of the transplanted kidney function. Concentration values are used in mathematical equations for GFR (glomerular filtration rate) calculation, with MDRD (modification diet in renal disease) being most commonly used. Cystatin C is an alternative marker for changes in glomerular filtration, which is also used in eGFR (estimated GFR) formulas. The aim of this study was to reveal eGFR <60 ml/min/1.72 m(2) in a population of patients after renal transplant, with stable graft function, using different formulas. MatERIAL AND METHODS: A group of 100 patients (56 females and 44 males) aged 20-78 years, took part in this study. Renal transplantation was conducted from 10 years to 10 months prior to the study. Estimated GFR was calculated with 4 formulas: MDRD, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), CKD-EPI cys (using cystatin C), and CKD-EPI mix (using creatinine and cystatin C). We used electronic calculators available on the National Kidney Foundation and the Nephron Information Center websites. RESULTS: The occurrence of eGFR values <60 ml/min/1.73 m(2) was 28% according to MDRD formula, 23% according to CKD-EPI, 25% according to CDK-EPI cys, and 26%according to CDK-EPI mix. CONCLUSIONS: Occurrence of GFR <60 ml/min/0.73 m(2) was the highest when calculated by MDRD formula, and the lowest when calculation was done with CDK-EPI. The significant discrepancy with different eGFR formula testing suggests the need for further research to find the best marker and/or formula for graft function estimation.