Abstract 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.
Abstract 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.
ObjectiveLight chain deposition has been shown to be an important histologic hallmark with differences in isotype, characteristics and ratio of kappa and lambda light chains having a significant role ...in pathobiology, pathogenesis and prognosis of several glomerular diseases. However, there is, to the best of our knowledge, no study dedicated to evaluating light chain deposits in patients with lupus nephritis (LN).MethodsWe have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of light chain deposition profile in the kidney of subjects with LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microscopy). Lambda domination (LD) was defined as lambda intensity – kappa intensity ≥ +1. SLE was diagnosed using the ACR criteria and renal outcomes per KDIGO.ResultsA total of 56 patients with LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38±13 years). Mean number of glomeruli per biopsy sample was 26±12. A total of 42 (75%) patients had light chain deposition in the glomerulus with 4 (7%) having restricted lambda chain deposition and none had restricted kappa chain deposition. Mean immunofluorescent intensity was 1.6±1.0 for lambda and 1.8±1.0 for kappa light chain. A total of 12 (21%) patients had LD in the glomerulus. When examining renal outcomes at one year post-biopsy, 55% of patients achieved complete response (CR), 30% achieved partial response (PR) and 15% had no response. There were no differences in achievement of remission (CR or PR) between patients with vs. without light chain deposition (88% vs. 71%, p=0.60) as well as between those with vs. without LD (90% vs. 83%, p>0.99).ConclusionLight chain deposition is prevalent in LN, but LD is much lower than in IgA nephropathy. While their deposition did not affect renal outcomes in our patients, light chains are an important factor to consider in LN patients, especially where restriction is present and further work-up, primarily for hematologic disease, is needed. Further investigation of the potential effect of pathobiologic characteristics of light chains in LN is warranted.
Introduction: Intrauterine growth restriction (IUGR) is linked to a higher incidence of cardiovascular and renal diseases. Methods: A total of 91 healthy individuals were included, 40 women and 51 ...men, born below the 10th percentile of birth weight for gestational age. Anthropometric parameters, arterial pressure (AP), blood glucose, estimated glomerular filtration rate (eGFR), albumin/creatinine ratio, lipid profile, uric acid, renal volume by ultrasound, pulse wave velocity, central arterial pressure (cAP), and augmentation index (Aix) were measured. Results: Men have higher body mass index (BMI), waist circumference, ambulatory and continuous AP, lower eGFR, pulse, higher uric acid and LDL cholesterol, lower HDL cholesterol, higher cAP and Aix, higher corrected renal volume, and birth weight than females. Overweight men had hypertension, lower eGFR, and dyslipidemia more often. Systolic pressure correlated positively with BMI in men. In women, systolic pressure correlated positively with heart rate and negatively with gestational age. BMI affected the systolic pressure in men and eGFR in women. Conclusion: Results indicate the more unfavourable effect of IUGR on men. Higher AP, vascular dysfunction, poorer renal function, and dyslipidemia predispose men to earlier chronic disease development. Key words: intrauterine growth restriction, arterial pressure, renal function
This study aimed to analyze blood pressure (BP) patterns, assess blood pressure variability (BPV), and its possible determinants in children with essential hypertension. The study group included 132 ...children with essential hypertension without antihypertensive therapy. Anthropometric and laboratory parameters were evaluated, office and ambulatory BP were measured. BPV was defined as the standard deviation of BP for the day and nighttime periods. In addition to classical statistical analysis, an unsupervised machine learning approach using the expected maximization algorithm was implemented to find groups of patients with similar characteristics. No differences in BPV were observed between sexes; however, boys had higher levels of creatinine, serum glucose, and uric acid despite similar body mass index values. There was a significant correlation between the Z-score for body mass index and daytime systolic BPV (r=0.19, p<0.05). Nighttime BPV significantly correlated with total cholesterol and uric acid levels. Within the male population, two clusters were found. The subjects in Cluster 2 had higher daytime and nighttime systolic and diastolic BP values, total cholesterol, triglycerides, and nighttime systolic and diastolic BPV. Our results suggest that the clustering of metabolic factors influences BPV in untreated children with essential hypertension, which may be a sex-specific effect in males. Key words: Blood pressure variability; Hypertension; Ambulatory blood pressure monitoring
Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Data on LN is scarce in the Croatian population. We analysed the characteristics of LN patients ...diagnosed at our tertiary referral centre. In this retrospective study, we analysed the following features of patients with biopsy-proven LN diagnosed between 2011 and 2020: demographics, renal laboratory parameters, renal histopathology, and treatment. A total of 38 patients were included (30 females; mean age 39+ or -15 years).The most common indication for kidney biopsy was proteinuria (89%). The proportion of LN classes was: class I (2.6%), II (5.3%), III (18.4%), IV (42.1%), V (13.2%), III+V (10.5%), IV+V (5.3%).The median time from SLE diagnosis to histologic confirmation of LN was 1.0 year. All patients were treated with methylprednisolone (MP), 68% received MP pulses. Induction treatment included intravenous (IV) cyclophosphamide (CYC) (71%) (15 patients treated per Euro-Lupus and 9 per the National Institutes of Health regimen), oral CYC (3%), or mycophenolate mofetil (11%). 79% of patients received antimalarials. While there is heterogeneity between different populations, our patient profile was similar to that from other European studies. Further follow-up of this group is necessary to assess outcomes in our population. Key words: systemic lupus erythematosus, lupus nephritis, treatment, population characteristics
•Fetal epigenetics determines telomere dynamics and health span in adulthood.•Environmental factors contributs to telomere length and dynamics.•Fetal telomere programing responds to environmental and ...physiological factors.
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.
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.
Uvod: IgA-nefropatija (IgAN) ima varijabilnu prezentaciju i prognozu. Međunarodni alat za predviđanje rizika u IgAN-u (IgAN-PT, od engl. International IgA Nephropathy Prediction Tool) predviđa ...napredovanje bubrežne bolesti do završnog stupnja ili smanjenje procijenjene glomerulske filtracije (eGFR) za 50%. Preporučuje se optimalna suportivna terapija najmanje tri mjeseca, praćena šestomjesečnom primjenom glukokortikoida samo u bolesnika s velikim rizikom napredovanja. Cilj: Istražiti koji su bolesnici imali veću vjerojatnost primiti imunosupresivnu terapiju (IS) te ishode liječenih IS-om. Ispitanici i metode: Retrospektivno kohortno istraživanje 48 bolesnika (33 muškarca), medijana dobi 50 godina (interkvartilni raspon, IQR, od engl. interquartile range 35 – 59), medijana praćenja 43 mjeseca (IQR 18 – 54), liječenih u Kliničkoj bolnici Merkur s novodijagnosticiranim idiopatskim IgAN-om u razdoblju od 2012. do 2021. godine. Rezultati: Imunosupresiju je primilo 17 bolesnika i oni su češće imali mezangijsku (M) (82% prema 54%, p=0,05), endokapilarnu hipercelularnost (E) (65% prema
21%, p=0,004) i polumjesece (C) (41% prema 14%, p=0,04). U odnosu na one bez IS-a nije bilo značajne razlike u eGFR-u kod biopsije (52 (IQR 38 – 81) prema 46 (IQR 30 – 72) ml/min/1,73 m2, p<0,05), ali su liječeni IS-om imali veću eGFR nakon dvije godine praćenja (66 IQR 37 – 97 prema 34 IQR 20 – 56 ml/min/1,73 m2, p=0,02). Omjer proteina prema kreatininu u urinu (uPCR) smanjio se nakon liječenja (kod biopsije, 106 IQR 50 – 317 prema završnom 47 IQR 20 – 129 mg/mmol), a nije bilo razlike u početnom i završnom uPCR između
onih koji jesu i nisu primali IS. Zbroj IIgAN se smanjio nakon liječenja (10,56% ± 12,66% prema 8,45% ± 9,22%, p=0,01), bez razlike u smanjenju između liječenih i neliječenih IS-om. Zaključci: Bolesnici s većim M, E i C su bili češće liječeni IS-om i oni su imali bolju eGFR nakon dvije godine; uPCR i zbroj IIgAN na kraju praćenja bili su manji neovisno o IS-u.
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