No abstract

No abstract

Increased serum 2PY concentration, along with a deterioration of kidney function and its toxic properties (significant inhibition of PARP-1 by 2PY), suggest that it could be a novel uremic toxin.

Hypertensive patients exhibit elevated cancer incidence, especially of cancers of the kidney. Elevated levels of ANG II, the active peptide of the renin-angiotensin system, regulating blood pressure and cardiovascular homeostasis, are known to cause hypertension and kidney diseases. There is evidence that ANG II is an activator of NAD(P)H oxidase, leading to the formation of free radicals, which are known to participate in the induction of DNA damage. This study was undertaken to characterize ANG II-induced DNA damage. DNA damage was measured by comet assay and micronucleus frequency test. Incubation of pig kidney cells (LLC-PK(1)) in vitro with ANG II concentrations between 85 and 340 nM led to a 6- to 15-fold increase of DNA damage compared with the control as revealed by comet assay analysis. Micronuclei were induced about fourfold compared with the control in pig and rat kidney cells (LLC-PK(1), NRK) and in human promyelocytic cells (HL-60). ANG II-induced DNA damage could be prevented by coincubation with the ANG II type 1 receptor blocker candesartan and the antioxidants N-acetylcysteine and alpha-tocopherol. The ANG II type 2 receptor antagonist PD123319 could not reduce ANG II-induced DNA damage. Measurement of reactive oxygen species (ROS) by flow cytometry showed an enhanced formation after exposure to ANG II and a reduction of ROS after candesartan, N-acetylcysteine, and alpha-tocopherol. The present findings support our hypothesis that ANG II causes DNA damage via ANG II type 1 receptor binding and subsequent formation of oxidative stress.

Taken together, SRL was shown to inhibit osteoclast formation in vivo and in vitro. SRL thus may have the potential to balance osteoclast promoting effects of glucocorticoids and CI, thereby counteracting the development of accelerated osteoporosis in renal transplant recipients.

Background: The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. Methods: Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. Results: Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. Conclusions: These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy.

Screening for and treating asymptomatic bacteriuria are common in KTRs despite uncertainties around the benefits and harms. In an era of antimicrobial resistance, further studies are needed to address the diagnosis and management of asymptomatic bacteriuria in these patients.

Background. The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods. FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400–600 µg/L) or lower (100–200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results. The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions. These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.