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Background: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification., Case Presentations: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6., Conclusions: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN., (© 2024. The Author(s).)

This study aimed to compare the renal resistive index (RI) as an early marker of renal damage between normoalbuminuric children with type 1 diabetes mellitus (T1D) and normal age-matched controls. A total of 76 children with T1D (aged 10-18 years) and 76 healthy age-matched controls were enrolled. Anthropometric parameters, blood pressure, glycated hemoglobin (HbA1c), serum creatinine (sCr), estimated glomerular filtration rate (eGFR), serum uric acid (SUA), urine albumin/creatinine ratio (ACR), and degree of pubertal development were determined in all participants. RI was measured using Doppler ultrasound in both groups. The T1D group had lower sCr and SUA values and higher ACR and mean RI values than the control group. Using the expectation-maximization method, 2 clusters of T1D patients were identified. Cluster 2 with higher RI values, eGFR and HDL cholesterol was more prone to albuminuria and could carry worse prognosis. In conclusion, renal RI is increased in the hyperfiltration phase of diabetic nephropathy in children with T1D. Renal RI could be helpful as a marker for diagnosing diabetic nephropathy in the early preclinical course of the disease in normoalbuminuric children with T1D., (Sestre Milosrdnice University Hospital.)

Allograft biopsy is a cornerstone in the management of transplanted kidneys. It is a safe procedure, often performed in the outpatient setting. A rare complication is formation of a postbiopsy arteriovenous fistula (AVF). We present here a report of two cases of postbiopsy AVFs treated endovascularly. Selective embolization is a safe and effective method of treatment of postbiopsy AVFs in renal allografts., Competing Interests: Conflict of Interest None declared., (International College of Angiology. This article is published by Thieme.)

Chronic kidney disease (CKD) is a serious illness with important consequences for patients and health systems. Estimation of prevalence and incidence, especially in early stages, is difficult due to a lack of epidemiological studies and consolidated registries. In general, the disease awareness is low, and thus CKD is not timely diagnosed in most cases. Robust screening programs are not implemented in Eastern European countries. A panel consisting of Primary Care Physicians and Nephrologists from Bulgaria, Croatia, Serbia, and Slovenia virtually met in December 2021 to discuss current CKD awareness and diagnostic approaches in the Balkan area The meeting resulted in specific calls to action in the region to improve the number and quality of epidemiology studies and the level of awareness among patients and medical communities, as well as implementation of screening programs in high-risk populations. Collaboration between specialists was acknowledged as a crucial driver for optimal management of patients with CKD. Joint efforts are required to persuade healthcare authorities to establish specific policies for better care of kidney patients.

Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice., (© 2021 Nada Božina, Lana Ganoci, Livija Simičević, Katarina Gvozdanović, Iva Klarica Domjanović, Margareta Fistrek Prlić, Tena Križ, Ana Borić Bilušić, Mario Laganović, and Tamara Božina, published by Sciendo.)

[This corrects the article DOI: 10.1155/2020/9480860.]., (Copyright © 2020 Vedran Premužić et al.)

IgA nephropathy (IgAN) is a rather uncommon complication of TNF-alpha inhibition with a range of findings such as asymptomatic microscopic/macroscopic hematuria or different degrees of proteinuria and could progress to end-stage renal disease. We are reporting three patients with longstanding rheumatoid arthritis (RA), which developed IgAN while receiving TNF-alpha inhibitors. All off our three patients had RA, which lasted 2-4 years, and none of them had a prior history of chronic kidney disease. Two patients were treated with adalimumab while one patient was treated with golimumab. Discontinuation of anti-TNF-alpha therapy and initiation of immunosuppressive therapy led to improvement in serologic abnormalities and renal function in two patients, while the third patient's 24-hour proteinuria was only partially reduced, which supports previous reports on TNF-alpha inhibitor induced autoimmunity. Two of our patients had previously been diagnosed with type 2 diabetes mellitus while the third patient developed diabetes years after the onset of IgAN. This is in line with the previously described association of IgAN and diabetes mellitus. To our best knowledge, this is the first report to analyze the development of IgAN as a potential consequence of anti-TNF-alpha therapy and its possible association with pretreatment or posttreatment diabetes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2020 Vedran Premužić et al.)

Advances in epigenetics now enable us to better understand environmental influences on the genetic background of human diseases. This refers especially to fetal development where an adverse intrauterine environment impacts oxygen and nutrient supply to the fetus. Recently, differences in telomere length and telomere loss dynamics among individuals born with intrauterine growth restriction compared to normal controls have been described. In this paper we propose possible molecular mechanisms that (pre)program telomere epigenetics during pregnancy. This programming sets differences in telomere lengths and dynamics of telomere shortening in adulthood and therefore dictates the dynamics of aging and morbidity in later life., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Varicella zoster virus (VZV) is distributed worldwide and is highly contagious. In adults and immunosuppressed patients of any age, the clinical course is much more severe. The most severe complications are pneumonia (the main cause of lethal outcomes in this infection), encephalitis, and very rarely Reye syndrome and hepatitis., Case Presentation: We present a 59-year-old man who came to the emergency department due to varicella and diarrhea. During initial evaluation acute kidney failure (AKF) was diagnosed, and the patient was admitted to the intensive care unit. Continuous renal replacement therapy was applied, and the patient was treated with acyclovir in adjusted doses; renal biopsy revealed acute tubular necrosis. Complete renal function recovery was established after 12 days., Conclusion: VZV infection occurs in a range of clinical scenarios, sometimes presenting only with mild symptoms, but in some other setting it can result in severe AKF even in healthy kidneys. Acute VZV infection can lead to isolated, clinically significant kidney failure. The administration of continuous renal replacement therapy and adjusted doses of acyclovir has a favorable effect on the course of the infection, with complete recovery of kidney function.

Regardless of having a similar antihypertensive effect, different antihypertensive drug classes have a different effect on albuminuria. Patients with albuminuria will usually need more than one drug to achieve blood pressure control, particularly if the aim is also to reduce albuminuria. Albuminuria is independently associated with cardiovascular and renal risk regardless of diabetes status. The recent ESC/ESH guidelines listed microalbuminuria among the hypertension-mediated organ damages. Albumin-to-creatinine ratio was suggested to be included in routine workup for evaluation of every hypertensive patient and changes in albuminuria were considered to have moderate prognostic value. Because of its specific effects on renal hemodynamic and glomerular structure, the ACEIs and ARBs should be prescribed in maximum tolerated doses. The MRAs can be considered in uncontrolled hypertensive patients. The CCBs can be used in addition to the RAAS blockade. Data on antialbuminuric effect of the new CCBs generation (T-type and N-type calcium channel blockers) is promising and they might be preferential CCBs when available. In case of resistant hypertension, thiazide or thiazide-like diuretic has to be added into the combination with RAAS blockers and other antihypertensive drugs. Low-salt intake has to be recommended for all hypertensive patients, particularly those with albuminuria. A multifactorial and early antialbuminuric approach should be started even when albuminuria values are below the cut-off value for microalbuminuria., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objectives: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed., Design, Setting, Participants, & Measurements: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal., Results: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02)., Conclusions: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time., (Copyright © 2015 by the American Society of Nephrology.)

The role of adiponectin in hypertension is still a matter of debate. Obtained conflicting results could be mostly explained with diversity of subjects included in different studies. Our aim was to analyze association of adiponectin with blood pressure (BP) in a group of normotensive and untreated hypertensive subjects. Participants (N=257) were selected from a random sample of 2487 subjects enrolled in an observational cross-sectional study. Subjects with diabetes and chronic kidney diseases were excluded. BP was measured using Omron M6 device following ESH/ESC guidelines. Adiponectin concentration was determined by ELISA. There were no differences in adiponectin values (mg/L) between hypertensives and normotensives (median 9.75; iqr: 7.44-17.88 vs 11.35; iqr: 7.43-12.63; P=0.17). On univariate linear regression adiponectin was not associated with systolic or diastolic BP (P>0.05). Furthermore, multivariate analysis did not show significant contribution of log-transformed adiponectin either to systolic (β=-0.040; P=0.43) or diastolic BP (β=0.066; P=0.33). In our group of normotensives and untreated hypertensives with normal kidney function adiponectin was not associated with BP even after adjustment for other risk factors. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Objective: Arterial stiffness is an independent cardiovascular risk factor. Aging, high blood pressure and increased renin-angiotensin system activity contribute to increased arterial stiffness in patients with atherosclerotic renovascular hypertension (aRVH). A literature search failed to identify any study related to this topic. Therefore, our aim was to determine the arterial stiffness in patients with aRVH and analyze whether stenting in addition to multifactorial drug therapy has beneficial effects on markers of stiffness and the clinical course., Methods: In this 6-month longitudinal study, 37 patients with refractory hypertension and unilateral aRVH were enrolled. After stenting, all patients received multifactorial dug therapy including 80 mg of telmisartan. Arterial stiffness indices were determined using Arteriograph. The control group consisted of 44 patients with essential hypertension., Results: There were no differences in brachial blood pressure values between the two groups (P > 0.05). At baseline, adjusted pulse wave velocity (PWV) was higher in aRVH patients than that of essential hypertensive patients (12.8 ± 0.4 vs. 11.6 ± 0.3 m/s; P = 0.029). In the aRVH group, at the end of the follow-up, a significant decrease in the aortic augmentation index (37.7 ± 9.9 vs. 33.7 ± 11.4; P = 0.02) without changes in PWV was observed (P > 0.05)., Conclusion: This study is the first to show that arterial stiffness is higher in patients with refractory aRVH than in those with essential hypertension. Multifactorial therapy based on stenting and intensive medical treatment reduced central blood pressure and augmentation index. Failure to obtain PWV reduction is likely a consequence of the present irreversible structural vessel changes. Longer follow-up might enable us to resolve whether arterial stiffness indices have better predictive ability in patients with aRVH than brachial blood pressure.

Objective: The mechanisms that increase cardiovascular risk in individuals born small for gestational age (SGA) are not well understood. Telomere shortening has been suggested to be a predictor of disease onset. Our aim was to determine whether impaired intrauterine growth is associated with early signs of vascular aging and whether telomere length could be a biomarker of this pathway., Methods: One hundred and fourteen healthy young men born SGA or after normal pregnancy [appropriate for gestational age (AGA)] were enrolled. Patient data were gathered from questionnaires and clinical exams, including blood pressure (BP) measurement routine laboratory analyses, and carotid intima-media thickness (cIMT). Leukocyte telomere length (LTL) was assessed by quantitative PCR. Birth data were obtained from medical records., Results: The SGA group had significantly higher pulse pressure and cIMT, and a trend to increased SBP and heart rate in comparison to the AGA group. Interestingly, SGA men exhibited a 42% longer LTL than the AGA group. LTL was inversely associated with age, BMI, BP and birth parameters. In multiple regression analysis, BMI was the key determinant of SBP and cIMT., Conclusion: Young men born SGA show early signs of vascular aging. Unexpectedly, in our cohort, the SGA group had longer telomeres than the normal controls. Although longer telomeres are predictive of better health in the future, our findings could indicate a faster telomere attrition rate and probable early onset of cardiovascular risk in SGA participants. Follow-up of this cohort will clarify hypothesis and validate telomere dynamics as indicators of future health risks.