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Abstract: In patients with end-stage renal disease (ESRD), bone disturbances are common. The aim of this study was to compare the bone mineral status in patients with ESRD, in patients post renal transplantation and in healthy controls. The groups were composed of 218 males and 126 females (ESRD), 43 males and 23 females (renal transplantation) and 614 males and 927 females (healthy controls). Skeletal status was evaluated by quantitative ultrasound measurements of the phalanges using a DBM 1200 (IGEA, Carpi, Italy), which measures the amplitude-dependent speed of sound (Ad-SoS) in m/s. Data analyses were performed with Statistica 6 for Windows (StatSoft, Inc., Tulsa, OK, USA). The Z-scores in gender subgroups were significantly lower in patients undergoing dialysis and after transplantation than in controls (p < 0.00001). The Z-scores did not differ between gender subgroups after transplantation and the Z-scores of dialyzed males were significantly better than in females (p < 0.00001). The mean value of Z-scores in patients after transplantation was significantly lower than in all patients with ESRD (p < 0.05) and in males (p < 0.01). The duration of dialysis negatively influenced the Ad-SoS; however, the time elapsed since transplantation did not. The cumulative corticosteroid dose did not correlate with skeletal variables. In conclusion, patients with ESRD treated with hemodialysis and postrenal transplantation patients, across both genders, were observed to have skeletal disturbances. (E-mail: osteolesna@poczta.onet.pl) [Copyright &y& Elsevier]

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension., (© 2024. The Author(s).)

Aims: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported., Methods and Results: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis., Conclusion: Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Transplant recipients have a significantly greater incidence of cancer, compared with the general population, who are referred to immunosuppressive therapy as an additional malignancy risk factor. Therefore, there is a need to search for an easy in clinical practice neoplasm predictor, especially for this group of patients., Materials and Methods: A group of 74 (43M and 31F; aged 46.8 ± 12 years) kidney transplant recipients was investigated in a three-year follow-up study. During the time of observation, 7 patients were diagnosed with neoplasm (7.4 ± 1.5 years after transplantation). A serum level of IL2 (ELISA test) and mRNA level of IL1beta, IL10 and TNFalfa in peripheral mononuclear blood cells - PBMCs (QRT - PCR method) were measured in every year of observation. Analysis of variances and t-Student test were used in groups mean comparison: N - patients developing malignant neoplasm group (24 probes); M - set of probes from patients with malignancies at the moment of diagnosis (11 probes); P - set of probes from patients before developing malignant neoplasm (10 probes); C - control group of healthy transplant recipients (31 probes)., Results: Among the analyzed agents, only serum IL2 level differed between the analyzed groups, with higher values in the M compared with the P group (p<0.05) and with C group (p<0.01). There were no differences neither between N and C or P and C groups (p = 0.98), nor any correlation between IL2 and IL1b, IL2 and TNFalfa., Conclusions: The results may indicate that IL2 serum level might be consider as a useful late unspecific cancer marker, although larger studies should yield verification of this finding.

Introduction: Transforming growth factor β1 (TGF-β1) is a cytokine involved in the process of pathological tissue sclerosis, which is part of the pathophysiological mechanism of end stage renal disease development. The aim of the study was to evaluate the association of the single nucleotide polymorphism rs1800471 of the TGFB1 gene with chronic kidney disease (CKD) occurrence and progression as well as hypertension appearance., Material and Methods: It was a case-control study where 109 patients with CKD and 111 very old people were enrolled. The association of the studied polymorphism with mentioned diseases was assessed in the whole study group as well as in the subgroups stratified according to the underlying etiology of CKD: nephropathy in type 1 diabetes (n = 13), chronic glomerulonephritis (n = 50) and chronic interstitial nephritis (n = 46)., Results: No association of CKD progression with rs1800471 polymorphism was observed. The C allele was identified as the one associated with higher risk of the disease occurrence in the dominant model of inheritance (p = 0.035). The C allele in women, opposite to male gender, was associated with higher risk of CKD development (p = 0.038). GG genotype was associated with elevated risk of hypertension appearance (p = 0,0021)., Conclusions: Due to the lack of accordance with previously performed studies it is still impossible to state an unequivocal conclusion regarding the association between rs1800471 polymorphism of the TGFB1 gene and risk of CKD occurrence and progression as well as hypertension appearance. That is why it is necessary to perform further studies in this field.

In the course of chronic kidney disease, bone metabolism disturbances occur and become aggravated simultaneously with the progression of renal disorder, worsening patients' quality of life. We conducted a 4-year follow-up to assess phalangeal quantitative ultrasound (QUS) measurements in 32 patients undergoing chronic hemodialysis (17 males and 15 females) whose mean ages were 56.3 ± 15.2 years. The QUSs of hand phalanges were performed using DBM 1200 (IGEA, Carpi, Italy) and are expressed as amplitude-dependent speed of sound (Ad-SoS), Z-scores, and T-scores. In comparison with the age-, sex-, and body mass index-adjusted control group, QUS parameters were significantly decreased in all patients undergoing dialysis. During the 4-year follow-up, Ad-SoS and T-scores in all study groups sloped significantly with time. The significant negative relationships between follow-up Ad-SoS results and both baseline and follow-up parathormone values were demonstrated. Our results confirm a high prevalence of bone disturbances in patients undergoing chronic hemodialysis, and they do not improve during renal replacement therapy. The parathormone level seems to be an important agent in influencing bone status, but further studies are needed to understand the other risk factors in kidney-related bone disease., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Aims: To compare the quality of life of end stage renal disease (ESRD) diabetic and non-diabetic patients undergoing chronic haemodialysis., Methods: A case-control study of 54 diabetic and 60 non-diabetic patients undergoing maintenance haemodialysis. All subjects completed the Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.3 questionnaire as well as the SF-36 Health Survey (SF-36)., Results: When compared to the control non-diabetic group, physical health was significantly impaired in diabetic dialysis patients (P<0.005) and staff encouragement was significantly worse (P<0.05). In both groups, all other compounds of the SF-46 and variables related to kidney disease were similar., Conclusions: To improve diabetic haemodialysis patients' quality of life, physical activity should be incorporated to the routine dialysis care and health care professionals should support them more intensively., (J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart * New York.)

Background: Glucose has been the main osmole used in conventional peritoneal fluids (PDFs) since the beginning of continuous ambulatory peritoneal dialysis (CAPD). There is much concern regarding the possible risk to the good level of glycemia control lately observed. The aim of this study was to analyze, with the use of 72-hour continuous glucose monitoring system (CGMS), the influence of PDFs containing supra-physiological glucose concentrations on daily glucose profile in patients with end stage renal disease (ESRD) undergoing CAPD therapy., Material/methods: There were 30 diabetic and non-diabetic patients on CAPD using conventional 1.36% or 2.27% glucose PDFs examined in the study, with a control group of 13 healthy volunteers. All participants underwent 72-hour CGMS and HbA1c evaluation. There was the whole area under the curve (AUC) of each 24-hour glucose profile and of glucose excursion above 90 mg/dl estimated., Results: The high transport status appeared to significantly influence the mean maximum glucose value and its increment following peritoneal exchange (PE) in the study group and in a subgroup of diabetic patients, whereas in non-diabetics the mean 24-hour glucose concentration was importantly influenced. The percentage of glucose levels in the range above 90 mg/dl was significantly influenced by higher glucose concentration in the PDFs, as well as higher peritoneal transport status., Conclusions: The outcomes indicate that dialysate glucose concentration, as well as type of peritoneal transport, influence the occurrence of persistent hyperglycemia state, and suggest that CAPD may predispose to appearance of glycemic disorders.

Background: Cardiovascular disease is the most common cause of morbidity and mortality among long-term renal transplant recipients, and hyperlipidemia is an important risk factor for the development of cardiovascular and peripheral vascular disease. The prevalence of post-transplantation hyperlipidemia ranges from 16% to 78% of recipients. Lipid-lowering strategy with the use of statins has been shown shown to reduce the cardiovascular risks related to hyperlipidemia, but concomitant use of HMG-CoA reductase inhibitors and cyclosporine A may increase the risk of rhabdomyolysis or myoglobinuric acute graft failure due to drug-drug interactions with cyclosporine A., Case Report: We describe the case of a 53-year-old woman, a renal transplant recipient, who developed rhabdomyolysis following simvastatin lipid-lowering therapy. Immunosuppressive treatment included cyclosporine A, azathioprine and prednisone. After 32 days of simvastatin treatment she was hospitalized for profound muscle pain and weakness with a rise in serum creatine kinase to 60.000 IU/l and serum creatinine to 147 Kmol/l. No further deterioration in renal graft function during hospitalization was observed. 10 days after simvastatin was stopped and the daily CyA dose was reduced the patient was asymptomatic, with serum creatine kinase 67 IU/l and serum creatinine level within normal range., Conclusions: Renal transplant recipients treated with cyclosporin A, and also receiving statins for postransplantational hyperlipidemia, as well as for the prophylaxis of chronic rejection, should be monitored carefully both for CyA blood levels and for possible muscle toxicity.

The resorption and osteogenesis equilibrium is commonly known basal condition of bone tissue homeostasis. For the purpose of bone turnover analysis in the group of good controlled diabetic patients without any diabetic complications basal biochemical parameters of osteogenesis and resorption were estimated. During low-calcium diet conditions both serum concentration and urine excretion of creatinine, hydroxyproline, hydroxylysine and uric acid were investigated. Serum alkaline phosphatase activity and oxalic acid urine excretion were also measured. As the result of the study the higher serum alkaline phosphatase activity and hydroksyproline urine excretion in type 1 diabetic patients as well as higher hydroxyproline and hydroxylysine urine excretion in type 2 diabetic patients were found.

Both high morbidity and potentiation of systemic complications emphasise significance of diabetes mellitus and hypertension co-incidence. The aim of the study was to analyse the influence of hypertension accompanied with type 2 diabetes mellitus on calcium phosphorus and magnesium metabolism. The study was performed in standard low-calcium diet conditions on the group of 49 patients with type 2 diabetes mellitus (among them 27 had hypertension), 14 patients with essential hypertension and 20 healthy persons. Both serum and urine concentration of creatinine, calcium, phosphorus, hydroxyproline, hydroxylysine and uric acid were analysed. Oral calcium load test was done. Serum alkaline phosphatase activity and oxalic acid urine excretion were also estimated. There were no significant differences between diabetic patients with and without hypertension as far as calcium, phosphorus or magnesium metabolism were concerned.