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

Historically, it takes an average of 17 years for new treatments to move 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. Now is the time 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 are diagnosed worldwide, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because it is often silent in the early stages. 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 the patient to the clinician to the 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.

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.

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.