Nephrotic syndrome may persist despite end-stage kidney disease and result in dyslipidaemia, thrombosis and a significantly increased cardiovascular risk. Treatment of refractory nephrotic syndrome ...includes surgical bilateral nephrectomy, renal artery embolization and pharmacologic nephrectomy.
We present a case of a haemodialysis patient with refractory nephrotic syndrome who underwent pharmacologic nephrectomy. The procedure decreased the patient's cardiovascular risk and enabled the patient to become a candidate for kidney transplantation.
In certain situations residual renal function may be harmful. In such instances, nephrectomy should be considered. Pharmacologic nephrectomy using nephrotoxic drugs is a non-invasive approach with least potential complications.
In 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and ...cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia.PURPOSEIn 2022 hypertensive disease was the second cause of death in Croatia. The crude prevalence of hypertension is increasing and still majority of hypertensive patients did not reach blood pressure and cholesterol goals Low awareness, and small number of treated and controlled patients point on poor adherence and even worse clinical inertia.Croatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions - '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies.MATERIALS AND METHODSCroatian Hypertension League (CHL) has started the permanent public health action Hunting the Silent Killer aiming to increase health literacy. In 2023 we decided to intensify program with two missions - '70/26', and 'Do you know what is your number?' aiming to achieve target values in 70% and in 50% of patients treated for hypertension and dyslipidaemia, respectively, by 2026. For the health care workers, the program will primarily involve digital education, and 'School of Communication in Hypertension'. In the second arm of the program, we will advise patients and general population to visit our educational website with important and useful information on how to improve bad lifestyle, how to proper measure blood pressure, why is it important to sustain in taking drugs etc. In 2026, the CHL will organise field research to assess the success of programs using the same methodology as we used in previous EH-UH studies.We will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy.CONCLUSIONWe will monitor and analyse trends in the management and control of patients treated for hypertension and dyslipidaemia. This will enable us to make an evidence-based conclusion how successful we were in increasing health literacy.
Endemic (Balkan) nephropathy is a chronic tubulointerstitial disease frequently accompanied by urothelial cell carcinomas of the upper urinary tract. This disorder has recently been linked to ...exposure to aristolochic acid, a powerful nephrotoxin and human carcinogen. Following metabolic activation, aristolochic acid reacts with genomic DNA to form aristolactam-DNA adducts that generate a unique TP53 mutational spectrum in the urothelium. The aristolactam-DNA adducts are concentrated in the renal cortex, thus serving as biomarkers of internal exposure to aristolochic acid. Here, we present molecular epidemiologic evidence relating carcinomas of the upper urinary tract to dietary exposure to aristolochic acid. DNA was extracted from the renal cortex and urothelial tumor tissue of 67 patients that underwent nephroureterectomy for carcinomas of the upper urinary tract and resided in regions of known endemic nephropathy. Ten patients from nonendemic regions with carcinomas of the upper urinary tract served as controls. Aristolactam-DNA adducts were quantified by 32P-postlabeling, the adduct was confirmed by mass spectrometry, and TP53 mutations in tumor tissues were identified by chip sequencing. Adducts were present in 70% of the endemic cohort and in 94% of patients with specific A:T to T:A mutations in TP53. In contrast, neither aristolactam-DNA adducts nor specific mutations were detected in tissues of patients residing in nonendemic regions. Thus, in genetically susceptible individuals, dietary exposure to aristolochic acid is causally related to endemic nephropathy and carcinomas of the upper urinary tract.
Endemic (Balkan) nephropathy (EN), a devastating renal disease affecting men and women living in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, is characterized by its insidious ...onset, invariable progression to chronic renal failure and a strong association with transitional cell (urothelial) carcinoma of the upper urinary tract. Significant epidemiologic features of EN include its focal occurrence in certain villages and a familial, but not inherited, pattern of disease. Our experiments test the hypothesis that chronic dietary poisoning by aristolochic acid is responsible for EN and its associated urothelial cancer. Using ³²P-postlabeling/PAGE and authentic standards, we identified dA-aristolactam (AL) and dG-AL DNA adducts in the renal cortex of patients with EN but not in patients with other chronic renal diseases. In addition, urothelial cancer tissue was obtained from residents of endemic villages with upper urinary tract malignancies. The AmpliChip p53 microarray was then used to sequence exons 2-11 of the p53 gene where we identified 19 base substitutions. Mutations at A:T pairs accounted for 89% of all p53 mutations, with 78% of these being A:T rightward arrow T:A transversions. Our experimental results, namely, that (i) DNA adducts derived from aristolochic acid (AA) are present in renal tissues of patients with documented EN, (ii) these adducts can be detected in transitional cell cancers, and (iii) A:T rightward arrow T:A transversions dominate the p53 mutational spectrum in the upper urinary tract malignancies found in this population lead to the conclusion that dietary exposure to AA is a significant risk factor for EN and its attendant transitional cell cancer.
Background
Carotid-femoral pulse wave velocity (c–f PWV) is a gold standard for the arterial stiffness measurement and important biomarker for the assessment of the cardiovascular (CV) risk. Recent ...studies have focused on 24-h measurements of arterial stiffness and estimated PWV (ePWV). The aim of this study is to analyze agreement of office c–f PWV measurements (SphygmoCor) with 24-h oscillometric measurements (Mobil-O-Graph and Arteriograph), and with ePWV.
Results
This study included 154 patients with primary hypertension (average age 38.75 ± 12.65). Arterial stiffness has been measured in the office with SphygmoCor and 24 h with two oscillometric methods (Mobil-O-Graph and Arteriograph). ePWV was calculated using validated equation. PWV values obtained in office (SphygmoCor) showed higher average values compared to both 24-h oscillometric measurements of PWV and ePWV. The mean values of 24-h PWV measured by Arteriograph were higher compared to values obtained with Mobil-O-Graph. The measurement of PWV over 24 h using the Arteriograph is the most accurate among the methods that were compared with the office PWV measurements (accuracy of 0.989). However, the most precise method was the Mobil-O-Graph (0.631), and the highest degree of agreement also was shown with the Mobil-O-Graph (concordance coefficient correlation (CCC) = 0.447). The smallest deviation (TDI) and the highest probability of overlapping (CP) were observed with ePWV (TDI = 45.524, CP = 0.322, respectively).
Conclusion
In our group of young treated mild hypertensive patients with low CV risk, we found weak agreements between cfPWV and 24-h PWV. These methods are not interchangeable.
Abstract
Background: Chronic kidney disease (CKD) has a global prevalence of 9.1–13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, ...increasing the burden of both diseases. Summary: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. Key Messages: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.
Renal denervation (RDN) as a method of treating arterial hypertension (AH) was introduced in Croatia in 2012. A multidisciplinary team and a network of hospitals that diagnose and treat patients with ...severe forms of AH were established, and a very strict diagnostic-treatment algorithm was prepared. At monthly meetings patients with truly resistant hypertension who were candidates for RDN were discussed. According to the 2021 ESH position statement and 2023 ESH guidelines, RDN is considered an alternative and additional, not a competitive method of treating patients with various forms of AH which must be performed by following a structured procedure and the patient's preference should be considered. In view of the changes in the global scientific community, the Croatian Hypertension League brings this consensus document on RDN conducted with radiofrequency-based catheter, the only currently available method in Croatia. In this document, exclusion and inclusion criteria are shown, as well as three groups of patients in whom RDN could be considered. The new diagnostic-treatment algorithm is prepared and follow-up procedure is explained. In Croatia, RDN is reimbursed by the national insurance company, thus pharmacoeconomic analyses is also shown. Criteria required by an individual centre to be approved of RDN are listed, and plans for prospective research on RDN in Croatia, including the Croatian registry for RDN, are discussed.
Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is ...considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10sup.−3 × age2 − 2.621 × 10sup.−5 × age2 × MBP + 3.176 × 10sup.−3 × age × MBP − 1.832 × 10sup.−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
Background: Kidney transplantation is considered the best modality for renal replacement therapy. The use of immunosuppressive therapy and pre-existing and newly developed comorbidities predispose ...these patients to the use of a large number of medications. (Hyper)polypharmacy is associated with worse adherence and negative outcomes. This study aims to explore the factors correlated with hyperpolypharmacy and complex medication regimens in kidney transplant recipients. Methods: This is a cross-sectional study of outpatient kidney transplant recipients. Collected data include demographic data, complete chronic medication lists, medical history, and graft function. Linear and logistic regression were used to identify factors associated with hyperpolypharmacy and complex medication regimens. Medication regimen complexity was quantified by the Medication Regimen Complexity Index (MRCI). Results: Overall, 224 kidney transplant recipients were included, with an average time since transplantation of 8 years. Hyperpolypharmacy was present in more than two-thirds of patients; the average number of different medications was 12; and the mean MRCI score was 21.4, ranging from 6 to 50. Hypertension was almost universally present, while other frequently prescribed medication groups were hypolipemics, medication for bone-mineral metabolism disorders, gout, and antihyperglycemics. Conclusions: Factors independently associated with hyperpolypharmacy and complex medication regimens were found to be age and graft function. Studies investigating interventions aimed at reducing medication complexity and increasing adherence should focus on older patients with worse graft function.
Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs ...underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC‐specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC‐specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA‐specific mutational signature SBS22, with 68% to 76% AA‐specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC‐specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN‐associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine‐based screening of AAN patients for cancer presence and recurrence.
What's new?
Ingestion of aristolochic acid (AA) via contaminated wheat‐containing food products is a major cause of endemic neuropathy and urologic carcinogenesis in southeastern Europe. Here, using integrated multi‐omics analysis, the authors identified molecular programs underlying upper tract urothelial tumors (UTUC) in patients in Southern Europe with past carcinogenic AA exposure. Analyses reveal associations between 89 miRNAs and 1,862 target mRNAs, with confirmation of UTUC‐specific transcripts at protein level. AA‐specific mutations in UTUC and deleterious mutations were uncovered at both gene and transcript levels. The findings suggest that tumors in the urinary tract can be monitored by urine miRNA signature.
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