Mind the Gap in Kidney Care: Translating What We Know Into What We do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary-care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the gap in kidney care: Translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Mind the Gap in Kidney Care: Translating What We Know Into What We Do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay. DOI: 10.52547/ijkd.8216.

Mind the gap in kidney care: translating what we know into what we do.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Kidney health for all: preparedness for the unexpected in supporting the vulnerable.

As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year's World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.

Occurrence and prevention of iodinated contrast agent-induced kidney injury in light of the newest literature data: Time to change our clinical practice! / Radiojód kontrasztanyagok által okozott vesekárosodás és megelozése az újabb irodalmi adatok tükrében: Változtassunk a gyakorlaton!

Összefoglaló. A jelenlegi hazai gyakorlatban sokszor indokolatlanul korlátozzák a vesebetegek kontrasztanyagos vizsgálatát, és halasztódik a metformint szedok vizsgálata is, kontrasztanyag által okozott akut vesekárosodástól (contrast-induced acute kidney injury, CI-AKI) tartva. Összefoglalónk célja az ezzel kapcsolatos újabb ismeretek áttekintése és egy szakmai javaslat ismertetése annak érdekében, hogy a betegellátás szempontjából fontos vizsgálatok ne maradjanak el, ugyanakkor azok a maximális betegbiztonság jegyében készüljenek. Az elmúlt évek tanulmányai alapján a CI-AKI elofordulása a korábbinál kevésbé gyakori, és jelentosen különbözo a kontrasztanyag intravénás vagy intraarteriális alkalmazásától függoen. Legfontosabb rizikótényezoje a csökkent glomerulusfiltrációs ráta (GFR), mely stabil állapotú vesebetegnél, intravénás kontrasztanyag adásakor 30 ml/min/1,73 m2 alatt, intraarteriális alkalmazásakor 45 ml/min/1,73 m2 alatt képez magas rizikót. Proteinuria esetén a CI-AKI és a kontrasztanyaggal társult akut vesekárosodás (contrast-associated kidney injury, CA-AKI) kockázata is nagyobb, ezért a számított GFR mellett indokolt a vizelet albumin/kreatinin vagy fehérje/kreatinin hányados meghatározása is a vizsgálat elott. Az instabil állapot, az akut veseelégtelenség mindenkor magas kockázatot jelent, ilyenkor a számított GFR pontatlan, nem használható. Csökkent vesefunkció mellett figyelni kell a beadott kontrasztanyag mennyiségére, a vizsgálat 48-72 órán belüli ismétlésének kerülésére, a nemszteroid gyulladásgátlók vagy más nephrotoxicus szerek lehetoség szerinti szüneteltetésére. Prevenciós intézkedés a magas rizikóval bíró betegek esetében javasolt intravénás hidrálás formájában, fiziológiás koncentrációjú nátrium-klorid vagy nátrium-bikarbonát infúziójával. Az egyéb eljárások hatástalanok, és nem indokolt a beavatkozás utáni dialízis végzése sem végstádiumú veseelégtelen betegekben. A metformint 60 ml/min/1,73 m2 feletti eGFR-rel rendelkezo beteg vizsgálata kapcsán szükségtelen elhagyni, ettol rosszabb vesemuködés esetén kell szüneteltetni. Amennyiben a vizsgálat indikációja sürgosségi, az a metformin egyideju elhagyásával elvégezheto, de a gyógyszer csak 48 óra múlva, az akut vesekárosodás kizárását követoen adható vissza. Orv Hetil. 2022; 163(3): 83-91. Summary. In the current clinical practice, studies with iodinated contrast agents are often limited in patients with kidney disease and delayed in those on metformin therapy due to fear of contrast-induced acute kidney injury (CI-AKI). We aim to review the most recent information about CI-AKI and provide recommendations in order to avoid cancellation of important contrast-enhanced tests, but maximize safety considerations. According to the most recent findings, CI-AKI occurs less frequently nowadays than previously, and depends significantly on the route of contrast administration (intraarterial or intravenous). The most important risk factor is the decreased GFR, which, in stable patients with intravenous contrast administration provides high risk if the eGFR is less than 30 ml/min/1.73 m2, and with intraarterial contrast is less than 45 ml/min/1.73 m2. In patients with proteinuria, the risk of both CI-AKI and CA-AKI (contrast-associated kidney injury) is increased, therefore urinary albumin/creatinine or protein/creatinine ratios are recommended to measure before the contrast material administration, beside the eGFR determination. Unstable condition, acute renal failure always mean high risk; in these cases, eGFR calculation is imprecise and useless. If renal function is decreased, the amount of contrast material needs consideration, repeated contrast-enhanced studies should be avoided in 48-72 hours, the non-steroidal anti-inflammatory agents and other nephrotoxic drugs have to be discontinued. For high risk patients, preventive intravenous hydration should be given, either by physiologic saline or sodium bicarbonate infusion. Other drugs aiming prevention have proved to be useless; dialysis treatment immediately after contrast administration in end-stage renal disease patients is unnecessary. There is no indication to discontinue metformin if eGFR is higher than 60 ml/min/1.73 m2, but if the patient has less than that value, the metformin needs to be stopped. In urgent studies with contrast agent, metformin administration has to be discontinued simultaneously with the intervention, and this drug can only be readministered after ruling out acute kidney injury in 48 hours following contrast exposure. Orv Hetil. 2022; 163(3): 83-91.

Multidisciplinary education and lifestyle camps for CKD patients and their closest family members: effects on disease progression, self-management and psychosocial condition-a retrospective cohort study.

BACKGROUND: Multidisciplinary education including psychosocial care (MDE) may alleviate high burden of chronic kidney disease (CKD). Family support also has utmost importance, yet, MDE has rarely been provided jointly for patients and their relatives. METHODS: We organized intensive, 1-week-long boarding MDE and lifestyle camps for CKD stage III-V patients and their relatives and assessed the rate of CKD progression, proportion of participants' home-based dialysis choice, transplant activity, and improvement of their coping and attitude evaluated by written narratives. Outcome was compared to 40 controls with similarly advanced CKD, under standard of care on our outpatient clinic. RESULTS: In 60 predialysis patients, serum creatinine 12 months before participation was 281 [IQR 122] µmol/l, right before MDE 356 [IQR 141] µmol/l, 12 months after MDE 388 [IQR 284] µmol/l, eGFR decreased from 18.5 [IQR 10] ml/min to 14.0 [IQR 7] ml/min and 13.0 [IQR 8] ml/min, respectively. Twelve months' changes before and after MDE differed significantly (p = 0.005 for creatinine; p = 0.003 for eGFR). Decreased progression was found in comparison to controls (p = 0.004; 0.016, respectively) as well. During follow-up, MDE patients compared to controls chose PD as dialysis modality more often (p = 0.004), and were more active in renal transplantation (p = 0.026). Based on narratives, MDE enhanced participants' disease-specific knowledge and ability for coping. It also improved sympathy, helpfulness, and the mutual responsibilities of family members. CONCLUSIONS: Our unique MDE programme with participation of the closest relatives enhanced the effectiveness of education and strengthened family support, which contributed to favorable CKD outcome, increased activity in home-based dialysis selection and transplant activity.

FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy.

Background: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data. Methods: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR). Results: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters. Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

Investigation of lifestyle difficulties in dialysis patients using quantitative testing methods / Dializált betegek életviteli nehézségeinek megismerése kvantitatív vizsgálómódszerekkel.

Összefoglaló. Bevezetés: A krónikus vesebetegség tünetei, a kezelés sajátosságai nagymértékben korlátozzák a páciensek mindennapi életvitelét, hatással vannak testi és lelki egészségükre, és nehezítik társas kapcsolataikat. Célkituzések: A jelen kutatás célja a magyar dializált betegpopuláció egészségmuveltségének, életminoségének és betegségterhének megismerése, továbbá a kezelési típusok hatását kívántuk felmérni a fent említett pszichológiai tényezok mentén. Módszer: A vizsgálatban 42 krónikus dializált személy vett részt: 31 hemodializált és 11 hasi dialízist végzo vesebeteg. Átlagéletkoruk 63,33 ± 12,92 év. A minta életkor, nemi eloszlás és családi állapot alapján reprezentatív. Kérdoíves technikával mértük a betegek életminoségét, egészségmuveltségét és betegségterhét. Eredmények: Eredményeink szerint a peritonealis dialízist végzo betegek szignifikánsan magasabb egészségmuveltséggel rendelkeznek, mint hemodializált betegtársaik. Ez a jelentos különbség az életminoségük több területén is kimutatható volt. Következtetés: Eredményeink a betegedukáció és a kezeloszemélyzettol kapott támogatás (bátorítás) jelentoségére hívják fel a figyelmet. A betegoktatás a hemodializált betegcsoport esetében is kiemelten fontos. A klinikai szempontból hasznos intervenciós javaslatokat fogalmaztunk meg, melyek célzottan az egészségmuveltség fejlesztésére irányulnak. Orv Hetil. 2021; 162(30): 1208-1215. INTRODUCTION: The symptoms of chronic kidney disease, the peculiarities of the treatment greatly limit the patients' daily life, affect their physical and mental health and make their social relationships more difficult. OBJECTIVE: The purpose of this research is to explore the health literacy, the health-related quality of life and illness intrusiveness of Hungarian dialysis patients. Furthermore, we wanted to assess the effect of treatment types along the psychological factors mentioned above. METHOD: The sample consisted of 42 patients with chronic kidney disease, 31 of whom have hemodialysis and 11 have peritoneal dialysis treatment. Their mean age was 63.33 ±12.92 years. The sample is representative by age, gender, and marital status. We measured the health-related quality of life, the health literacy and illness intrusiveness of the patients using special questionnaire techniques. RESULTS: The peritoneal dialysis patients have significantly higher health literacy than their hemodialysis counterparts. This significant difference was seen in several areas of their quality of life as well. CONCLUSION: Our results draw attention to the importance of patient education and the special support by the treatment staff. The patient education for the haemodialysis group is of paramount importance for the hemodialysis group, too. We have formulated clinically useful intervention proposals aimed at improving health literacy. Orv Hetil. 2021; 162(30): 1208-1215.

Overcoming barriers and building a strong peritoneal dialysis programme - Experience from three South Asian countries.

The development of peritoneal dialysis (PD) programmes in lower-resource countries is challenging. This article describes the learning points of establishing PD programmes in three countries in South Asia (Nepal, Sri Lanka and Pakistan). The key barriers identified were government support (financial), maintaining stable supply of PD fluids, lack of nephrologist and nurse expertise, nephrology community bias against PD, lack of nephrology trainee awareness and exposure to this modality. To overcome these barriers, a well-trained PD lead nephrologist (PD champion) is needed, who can advocate for this modality at government, professional and community levels. Ongoing educational programmes for doctors, nurses and patients are needed to sustain the PD programmes. Support from well-established PD centres and international organisations (International Society of Peritoneal Dialysis (ISPD), International Society of Nephrology (ISN), International Pediatric Nephrology Association (IPNA) are essential.

Outcome of patients with lupus nephritis under long-term immunonephrological care / Tartós immunonephrológiai gondozásban részesült lupus nephritises betegeink hosszú távú kezelési eredményei

INTRODUCTION: Lupus nephritis is the most severe complication of systemic lupus erythematosus (SLE), its development and the effectiveness of immunosuppressive therapy substantially influence patients' quality of life and survival. AIM: In this retrospective observational investigation, the long term-outcome of patients with lupus nephritis, followed at the St. Margit Hospital Immunonephrological Outpatient Clinic, was evaluated. RESULTS: Between 1997 December 1 and 2019 April 30, 73 patients (age 33.7 ± 15 years, 82% female, 18% male) were under care with median observation of 119 [between 3-264] months. At diagnosis, eGFR showed 68 [7-120] ml/min, proteinuria was 2800 [23-16812] mg/day; 10 patients needed dialysis treatment acutely. Renal biopsy, performed in 68 patients, proved proliferative lupus nephritis in 55 and pure membranous lupus nephritis in 6 patients. Administering combined immunosuppressive therapy, complete remission was achieved in 50 and partial remission in 21 cases; one or repeated relapses developed in 28 subjects. Two patients, by the time they got under our care, had already required chronic dialysis, and in the long term, three more patients progressed to end-stage renal disease requiring renal replacement therapy. Renal function stabilized in all other participants, clinical activity of SLE, SLEDAI score, complement levels and immunserology results improved significantly. CONCLUSIONS: Lupus nephritis can be effectively treated by combined induction and prolonged maintenance immunosuppression, but to prevent progression of the disease, long-term care is necessary by co-operation of nephrologist and immunologist. To provide adequate prevention and therapy of the SLE's multiorgan involvement and also the potential complications of immunosuppression, multidisciplinary team is needed with all specialists who may facilitate these patients' complex care. For the long-term management of patients with lupus nephritis, the nephrologists have to be responsible, and the multidisciplinary teams also have to be under their direction. Orv Hetil. 2020; 161(31): 1293-1301.

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

BACKGROUND: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. METHODS: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. RESULTS: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. CONCLUSIONS: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy.

BACKGROUND: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. RESULTS: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. CONCLUSIONS: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.

Simple, readily available clinical indices predict early and late mortality among patients with ANCA-associated vasculitis.

BACKGROUND: The early identification of patients with ANCA-associated vasculitis (AAV) who are at increased risk for inferior clinical outcome at the time of diagnosis might help to optimize the immunosuppressive therapy. In this study we wanted to determine the predictive value of simple clinical characteristics, which may be applicable for early risk-stratification of patients with AAV. METHODS: We retrospectively analyzed the outcome of 101 consecutive patients with AAV receiving a protocolized immunosuppressive therapy. Baseline Birmingham Vasculitis Activity Score (BVAS) and non-vasculitic comorbidities were computed, then predictors of early (<90 days) and late (>90 days) mortality, infectious death, relapse and end stage kidney disease (ESKD) were evaluated. RESULTS: The baseline comorbidity score independently predicted early mortality (HR 1.622, CI 1.006-2.614), and showed association with infectious mortality (HR 2.056, CI 1.247-3.392). Patients with BVAS at or above median (=21) had worse early mortality in univariable analysis (HR 3.57, CI 1.039-12.243) (p = 0.031), and had more frequent relapses (p = 0.01) compared to patients with BVAS below median. CONCLUSIONS: Assessing baseline comorbidities, beside clinical indices characterizing the severity and extension of AAV, might help clinicians in risk-stratification of patients. Future prospective studies are needed to investigate whether therapies based on risk-stratification could improve both short term and long term survival.

Therapy and prognosis of ANCA-associated vasculitis from the clinical nephrologist's perspective.

This paper reviews the recently published scientific information regarding ANCA-associated vasculitis (AAV), aiming to highlight the most important data from the clinical nephrologists' perspective. The classification, pathomechanism, recent achievements of the treatment, short-term and long-term outcomes of the disease, and the difficulties nephrologists face when taking care for patients with AAV are summarized. There has been significant progress in the understanding of the genetic and pathologic background of the disease in the last years, and results of histological studies guide us to predict long-term renal function. Findings of several multicentered trials with reasonable number of participants provide comparison of the efficacy and safety of different remission induction and maintenance therapies, and evaluate recently introduced immunosuppressive agents. Although the clinical outcome of patients with AAV has improved significantly since modern immunosuppressive drugs are available, the treatment-related complications still contribute to the morbidity and mortality. To improve the survival and quality of life of patients with AAV further, knowledge of the predictors of relapse, end-stage kidney disease, and mortality, also prevention of infections and other treatment-related adverse events are important. The eligibility for renal transplantation and the option for successful pregnancies for young women are also important factors which influence the patients' quality of life. In order to provide favorable outcome, the clinicians need to establish personalized treatment strategies to optimize the intensity and minimize the toxicity of the immunosuppressive therapy.

Genetic analysis and functional characterization of novel mutations in a series of patients with atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease-causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations.

Clinical outcomes of ANCA-associated vasculitis in elderly patients.

BACKGROUND: Older age is independently associated with mortality in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We hypothesized that a reduced-dose immunosuppressive treatment would result in similar effectiveness and comparable treatment-related morbidity in elderly patients as the regular dose in younger patients. We also postulated that the higher baseline comorbidities may contribute to the higher mortality of the elderly subjects. METHODS: Ninety-three consecutive patients with AAV between 1998 and 2012 were retrospectively analyzed. Forty-one individuals were defined as "elderly" (age >65 years) and 52 as "younger" (age <65 years). All cause and cardiovascular mortality, death due to vasculitis and infections, and effectiveness of "reduced-dose" immunosuppressive treatment in the elderly group were compared to the effects of "full-dose" treatment in younger individuals. RESULTS: Mortality in the elderly group was higher (p = 0.007). Cardiovascular death was significantly increased (p = 0.002) in the elderly, but mortality due to vasculitis or infections was comparable. Treatment effectiveness was also similar in elderly and younger patients. At the end of the first follow-up year, 37 % of the elderly and 27 % of the younger patients died (p = 0.22). In univariate Cox regression analyses, being older than 65 year, having cardiovascular disease at baseline, need for dialysis at diagnosis, and lower serum albumin were associated with an increased hazard of mortality. CONCLUSIONS: Delivering reduced dose of immunosuppression for elderly patients was associated with satisfactory outcome and favorable treatment-related complication profile. The higher mortality in the elderly could be attributed mainly to baseline cardiovascular morbidity.

Acute and long-term effects of corticosteroid therapy on bone metabolism in patients with kidney diseases.

AIM: The aim of our study was to examine parameters of bone metabolism during pulse and long-term methylprednisolone (MP) treatment in patients with kidney diseases. METHODS: In 13 patients with RPGN, treated with intravenous MP pulses, followed by tapering oral doses, osteocalcin (OC) and ß-CrossLaps (ß-CL) were measured before treatment, after the 3rd pulse, then 1 and 3 months later ("acute study"). In a separate set of analyses serum markers of bone metabolism and bone mineral density (BMD) were studied in 40 patients on maintenance MP therapy ("chronic study"). RESULTS: Immediately after the 3rd MP pulse serum OC decreased to 38 ± 23%, ß-CL increased to 200 ± 121% of the baseline (p = 0.002 for OC and p = 0.003 for ß-CL, respectively), and the OC/ß-CL ratio decreased from 55 ± 35 to 9 ± 7 (p = 0.002). OC remained below and ß-CL above baseline even at 3 months post pulse steroid treatment. Patients in the "chronic study" who were on maintenance oral steroid therapy received 13,844 ± 7,454 mg MP over 53 ± 47 months. BMD at the end of follow-up revealed reduced bone mineral density in 72.5% of the participants. Z-scores both at the hip and at the lumbar spine were significantly correlated with duration of steroid treatment and also with the cumulative steroid dose. CONCLUSION: MP pulse causes immediate, profound suppression of osteoblast function, and significant increase of osteoclast activity, suggesting uncoupling of bone formation and resorption. Prolonged high dose steroid treatment causes significant bone loss in patients with chronic kidney disease. Appropriate systematic follow up of bone metabolism, preventive measures and therapy when needed would be important for the bone health of this patient population.

[Role of plasmapheresis in immunological kidney diseases. Experience from 1050 completed plasmapheresis treatment sessions]. / A plazmaferézis szerepe immunológiai etiológiájú vesebetegségekben. Tapasztalataink 1050 elvégzett feréziskezelés kapcsán.

UNLABELLED: Plasmapheresis is an effective treatment modality in several immunological kidney diseases. It is also indicated in certain neurological and hematological abnormalities, and some other diseases. AIMS: In this study the indications and outcomes of the plasma exchange treatments performed in the Plasmapheresis Unit of the authors during the last 12 years are summarized, and the findings are compared to those published in the literature. The procedure, mechanisms of action and adverse effects are also briefly discussed. METHODS: Between 1999 and 2010 authors completed 1050 plasma exchanges in 195 patients with an average 5.4 (1-20) treatments/person. In the 78 males and 117 females (age 57±16 years) the indications were as follows: 47% anti-cytoplasmic antibody-associated vasculitis, 4% anti-glomerular basement membrane disease, 3% rapidly progressing immunocomplex glomerulonephritis, 11% severe complications of systemic lupus erythematosus, 1% treatment resistant focal segmental glomerular sclerosis, 5% hemolytic uremic syndrome, 13% complications of multiple myeloma, 4% HELLP syndrome, 10% neurological diseases, and 2% other abnormalities. RESULTS: Plasmapheresis, completed as part of combined immunosuppressive treatment, resulted in remarkable improvements in patients with anti-cytoplasmic antibody-associated vasculitis. Out of the 91 patients, 54 needed urgent dialysis on admission, and renal replacement therapy could be discontinued in 44% of them. Renal functions in those patients who did not need dialysis also improved significantly, and pulmonary hemorrhage ceased in all affected subjects. Survival of the patients with anti-glomerular basement membrane diseases was 100%. The treatment significantly improved the renal function in rapidly progressive lupus nephritis, and all the 5 cases of lupus cerebritis were successfully cured. The results showed less effectiveness in therapy resistant focal segmental glomerular sclerosis and in rapidly progressing immunocomplex glomerulonephritis. Plasmapheresis proved to be very efficient in cases with the primary hemolytic uremic syndrome, and each patient with HELLP syndrome recovered completely. The outcome of those with multiple myeloma was less favorable, although hyperviscosity was rapidly and effectively decreased by the plasmapheresis. The treatment improved the conditions of almost all patients with neurological diseases. DISCUSSION: According to these findings plasmapheresis treatment, introduced by proper indications, effectively improves the outcomes of several diseases. Early diagnosis and immediate introduction of the plasmapheresis are very important - in conjunction with the appropriate therapy of the underlying diseases.