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.
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.
Frailty is a pronounced symptom of aging associated with multiple comorbid states and adverse outcomes. The aim of this study was to evaluate the impact of 2 interventions, one based on prevention of ...falls and the other on prevention of loneliness, on total frailty and dimensions of frailty in urban community-dwelling elderly as well as associations with independent living.This prospective interventional study followed up 410 persons aged 75 to 95. The participants of the control and intervention groups were monitored through a public health intervention programme. The level of frailty was measured by the Tilburg Frailty Indicator (TFI) questionnaire and the factors of independent living were analyzed using validated questionnaires.After 1 year, physical frailty measured in the control group showed a statistically significant increase (r = -0.11), while in the intervention groups physical frailty did not increase (both P > .05). Psychological frailty measured after 1 year in the control group was significantly higher (r = -0.19), as well as in the group where the public health interventions to reduce loneliness were carried out (r = -0.19). Psychological frailty did not increase in the group in which public health interventions to prevent falls were carried out, and social frailty did not increase at all in the study period. The total level of frailty in the control group after 1 year was significantly increased (r = -0.19), while no increase was seen in the overall frailty in the intervention group. Multivariate analysis has shown that both interventions where independently associated with lower end frailty. Additionally, higher baseline frailty and visit to a physician in the last year were positively associated with higher end-study frailty level, while higher number of subjects in the household and higher total psychological quality of life (SF-12) were independently associated with lower end-study frailty. Only in the prevention of falls group there was no increase in restriction in the activities of daily living throughout study follow-up.Public health interventions to prevent falls and to prevent loneliness have a positive effect on the frailty and independent living of the elderly living in their own homes in an urban community.
Chronic kidney disease (CKD) is one of the major causes of morbidity and mortality, affecting >800 million persons globally. While we still lack efficient, targeted therapies addressing the major ...underlying pathophysiologic processes in CKD, findings of several recent trials have brought about a shifting landscape of promising therapies. The endothelin system has been implicated in the pathophysiology of CKD and endothelin receptor antagonists are one class of drugs for which we have increasing evidence of efficacy in these patients. In this review we summarize the most recent findings on the safety and efficacy of endothelin receptor antagonists in diabetic and non-diabetic CKD, future directions of research and upcoming treatments.
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
BK virus (BKV) is a polyomavirus with high seroprevalence in the general population with an unremarkable clinical presentation in healthy people, but a potential for causing serious complications in ...immunosuppressed transplanted patients. Reactivation or primary infection in kidney allograft recipients may lead to allograft dysfunction and subsequent loss. Currently, there is no widely accepted specific treatment for BKV infection and reduction of immunosuppressive therapy is the mainstay therapy. Given this and the sequential appearance of viruria-viremia-nephropathy, screening and early detection are of utmost importance. There are numerous risk factors associated with BKV infection including genetic factors, among them human leukocyte antigens (HLA) and killer cell immunoglobulin-like receptors (KIR) alleles have been shown to be the strongest so far. Identification of patients at risk for BKV infection would be useful in prevention or early action to reduce morbidity and progression to frank nephropathy. Assessment of risk involving HLA ligands and KIR genotyping of recipients in the pre-transplant or early post-transplant period might be useful in clinical practice. This review summarizes current knowledge of the association between HLA, KIR and BKV infection and potential future directions of research, which might lead to optimal utilization of these genetic markers.
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.
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.
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).
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.
PDF
