Association of deprivation and its individual domains on outcomes in people with chronic kidney disease.

Background: Due to the high correlation of chronic kidney disease (CKD) with other comorbidities, the sole effect of CKD on deprived people is not clear. In addition, there is a paucity of evidence in the literature linking isolated domains of deprivation to outcomes. This study aimed to examine whether deprivation was associated with adverse outcomes in patients with CKD, independent of cardiometabolic morbidities. Individual domains of deprivation were also evaluated. Methods: A retrospective study of patients with non-dialysis-dependent CKD (ND-CKD) in the Salford Kidney Study to investigate the association of deprivation with outcomes. The English Indices of Deprivation was used for the comparative analysis of the five quintiles of deprivation. Two propensity score methods were used to attenuate the confounding effect of cardiometabolic morbidities between the least and the most deprived groups. Results: People living in the least deprived areas (n = 319) had a lower risk of combined outcomes (all-cause mortality and renal replacement therapy) when compared with the most deprived group (n = 813) [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71-0.98]. The negative association of deprivation remained after matching but with mixed statistical significance when using different propensity methods (HR 0.85; 95% CI 0.70-1.03 for propensity score matching and HR 0.77; 95% CI 0.61-0.98 for inverse probability weighting). The association of combined outcomes varied across component index of multiple deprivation domains with wide CIs. However, areas with lower scores for education, income and employment were significantly associated with a higher risk. Conclusions: This study has identified that in people with ND-CKD, unemployment, poor educational attainment and lower household income were associated with poor outcomes. The association of deprivation with adverse outcomes persists despite adjustment for cardiometabolic morbidities.

Enhancing clinical service design for multimorbidity management: A comprehensive approach to joined-up care for diabetes, chronic kidney disease, and heart failure.

BACKGROUND AND AIMS: Multimorbidity is becoming the norm rather than the exception, especially among the ageing population and people with lower socio-economic status. In addition to the rising healthcare cost, multimorbidity poses considerable difficulty in the delivery of adequate holistic care for affected patients. METHODS: This review presents a discussion of the current barriers to delivering holistic care to people with multimorbidity and proposes a model of clinical care for people living with cardiovascular-kidney-metabolic (CKM) syndrome as an exemplar of a multimorbidity cluster. RESULTS: Single organ/disease services may not be able to provide optimum care to people with multimorbidity due to the potential complex interactions between multiple disease symptoms and management. In addition, people with multimorbidity may be required to attend multiple appointments in different healthcare centres. This may negatively impact access to services due to time and financial burden. Other barriers include co-ordinating communication between healthcare professionals and reduced continuity of care. Optimising CKM health requires patient-centred care led by an interdisciplinary care team who ideally should possess CKM competencies utilising a shared care protocol to coordinate evidence-based care and use of telehealth to empower patients. Stakeholders and policymakers need to adapt new policy models to establish and enhance CKM care models by allocating funds and implementing frameworks for educational reforms. CONCLUSIONS: A CKM service has the potential to increase the uptake of cardiac and renal protective medications as well as optimising metabolic care, increase capacity in both primary and secondary care, improve quality of life and clinical outcomes, reduce patient inconvenience, and importantly allow rapid translation of advances in cardiorenal metabolic diseases into clinical practice.

Increased risk of end-stage kidney disease in patients with chronic kidney disease and heart failure with reduced ejection fraction.

INTRODUCTION: The prevalence of heart failure (HF) is more common in people with advanced non-dialysis chronic kidney disease (ND-CKD). It is well known that HF with reduced ejection fraction (HFrEF) is associated with a higher risk of mortality in people with ND-CKD compared to the general population. However, the impact of HFrEF on progression into end-stage kidney disease (ESKD) is not well studied. Our study aimed to examine the independent association of HFrEF on progression to ESKD after correcting for confounding factors using two methods of propensity scoring. METHODS: This study used data from the Salford Kidney Study, a longitudinal study which has recruited more than 3000 patients with ND-CKD since 2002. Patients without a history of HF during the recruitment questionnaire were included in the control group. Patients with a reported history of HF and echo showing left ventricular ejection fraction <40% at enrolment were included in the HFrEF group. Two propensity score methods were used to attenuate the effects of confounding factors between the two groups - propensity score matching (PSM) and inverse probability weighting (IPW). Univariate and multivariate Cox regression analyses were performed. RESULTS: A total of 2383 patients were included in the analysis. Patients with HFrEF had significantly higher median age and a higher percentage of male gender compared to patients with no HF (72.5 vs 66.6 years and 71.8% vs 61.1% respectively). Univariate and 5 models of multivariate Cox regression analysis showed that HFrEF in people with CKD was a strong predictor for a higher incidence of ESKD (model 5: HR 1.38; 95% CI = 1.01-1.90; p = 0.044). The association between HFrEF and the risk of ESKD remained significant after using the PSM and the IPW methods. CONCLUSION: Patients with concomitant advanced ND-CKD and prevalent HFrEF were found to have a higher risk of ESKD when compared to patients with no HF. This risk persists despite the adjustment of confounding factors using PSM and IPW.

New therapeutic perspectives for vascular and valvular calcifications in chronic kidney disease.

PURPOSE OF REVIEW: Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies. RECENT FINDINGS: Conventional therapies targeted at CKD-mineral and bone disorder (MBD) modulation have yielded conflicting or inconclusive results. Magnesium and vitamin K supplementation appear to offer attenuation of coronary artery calcification but inconsistent findings justify the need for further studies. Strategies targeting hydroxyapatite formation such as sodium thiosulphate and hexasodium fytate show promise and are worthy of further evaluation. The serum calcification propensity assay (T50) correlates with severity and progression; it holds promise as a potential future clinical tool for screening monitoring calcification risk. SUMMARY: Whilst knowledge of the pathophysiology of vascular calcification has grown and therapeutic approaches appear promising, as yet no medication has been approved to treat vascular or valvular calcification, or calciphylaxis.

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Management of de novo nephrolithiasis after kidney transplantation: a comprehensive review from the European Renal Association CKD-MBD working group.

The lifetime incidence of kidney stones is 6%-12% in the general population. Nephrolithiasis is a known cause of acute and chronic kidney injury, mediated via obstructive uropathy or crystal-induced nephropathy, and several modifiable and non-modifiable genetic and lifestyle causes have been described. Evidence for epidemiology and management of nephrolithiasis after kidney transplantation is limited by a low number of publications, small study sizes and short observational periods. Denervation of the kidney and ureter graft greatly reduces symptomatology of kidney stones in transplant recipients, which may contribute to a considerable underdiagnosis. Thus, reported prevalence rates of 1%-2% after kidney transplantation and the lack of adverse effects on allograft function and survival should be interpreted with caution. In this narrative review we summarize current state-of-the-art knowledge regarding epidemiology, clinical presentation, diagnosis, prevention and therapy of nephrolithiasis after kidney transplantation, including management of asymptomatic stone disease in kidney donors. Our aim is to strengthen clinical nephrologists who treat kidney transplant recipients in informed decision-making regarding management of kidney stones. Available evidence, supporting both surgical and medical treatment and prevention of kidney stones, is presented and critically discussed. The specific anatomy of the transplanted kidney and urinary tract requires deviation from established interventional approaches for nephrolithiasis in native kidneys. Also, pharmacological and lifestyle changes may need adaptation to the specific situation of kidney transplant recipients. Finally, we point out current knowledge gaps and the need for additional evidence from future studies.

Mechanistic Links between Central Obesity and Cardiorenal Metabolic Diseases.

BACKGROUND: There is a marked increase in the global prevalence of obesity over the last decades with an estimated 1.9 billion adults living with overweight or obesity. This is associated with a sharp rise in prevalence of cardiorenal metabolic diseases such as type 2 diabetes mellitus, chronic kidney disease, and heart failure. With recent evidence of the efficacy of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal protection and weight reduction, it is reasonable to investigate common causative pathways for cardiorenal metabolic diseases. SUMMARY: Central obesity is a common condition with 41.5% prevalence worldwide. It is associated with adverse outcomes even in people with a normal body mass index. Central obesity develops when the personal fat threshold for expansion in the subcutaneous adipose tissue exceeds a certain level. Multiple factors such as age, gender, genetics, and hormones may play a role in determining personal susceptibility to central obesity. Cardiorenal metabolic diseases usually cluster in certain populations - commonly in people with central obesity - and cause a substantial burden on health services and increase the risk of all-cause mortality. In this review, we investigate the pathophysiological pathways between central obesity and cardiorenal metabolic diseases. These pathways include activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, inflammation and oxidative stress, haemodynamic impairment, insulin resistance, and endothelial dysfunction. KEY MESSAGE: Central obesity has a pivotal role in the development of cardiorenal metabolic diseases and should be targeted with population-based approaches, such as dietary and lifestyle interventions, as well as the development of pharmacotherapy to reduce the burden of cardiorenal metabolic diseases.

Mortality and Renal Outcomes Are Impacted by Obesity in Cardiorenal Metabolic Disease but Not in People with Concomitant Diabetes Mellitus.

INTRODUCTION: Mounting evidence in the literature describes a reverse association, whereby obesity may have a protective effect on mortality - the "obesity paradox." Due to the significant overlap between elements of cardiorenal metabolic disease, we examined the effects of obesity on outcomes in a cohort of patients with non-dialysis chronic kidney disease (ND-CKD) by grouping patients according to their level of cardiometabolic co-morbidity to reduce the risk of bias. METHODS: This study was undertaken on all patients with a documented body mass index (BMI) in the Salford Kidney Study database from October 2002 until December 2016. Patients were grouped according to their BMI into normal weight, overweight, and obese, and also according to their level of co-morbidity into 4 groups: group 1 had CKD only; group 2 had CKD and heart failure (HF); group 3 had CKD and diabetes mellitus (DM); and group 4 had CKD, DM, and HF. Univariate and multivariate Cox regression analyses were performed. RESULTS: A total of 2,416 patients were included in the analysis. The median age was 67.3 years, 61.8% were male, and 96.4% were Caucasian. Obesity was associated with a lower incidence of combined outcomes in patients with ND-CKD who did not have DM (hazard ratio [HR] 0.74; p = <0.001 and HR 0.48; p = 0.008 for CKD alone and CKD + HF groups, respectively). This protective effect remained significant after correcting for major factors. In patients with ND-CKD and DM, there was no difference in all-cause mortality between the normal weight group and the obesity groups. CONCLUSION: Obesity may be protective against adverse outcomes only in groups 1 (CKD alone) and 2 (CKD + HF). This "protective" effect was not seen in patients who had concomitant diabetes. These data suggest that diabetes is a potent predictor of adverse outcomes, irrespective of BMI; however, in patients without diabetes, obesity may play a protective role.

The epidemiology of primary FSGS including cluster analysis over a 20-year period.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre's 20-year experience of primary FSGS. METHODS: Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset. RESULTS: The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p<0.001) and higher median urine protein creatinine ratios (uPCR)- 795mg/mmol vs 318mg/mmol (p <0.001). They were more likely to achieve complete remission (62% vs 40%, p=0.041), but relapsed more 48.6% vs 22% (p=0.027). Overall 5 year mortality was 10.3% and 5 year progression to RRT was seen in 17.2%. Complete remission was observed in 49.4%. The 2-step cluster analysis separated the cohort into 3 clusters: cluster 1 (n=26) with 'nephrotic-range proteinuria'; cluster 2 (n=43) with 'non-nephrotic-range proteinuria'; and cluster 3 (n=18) with nephrotic syndrome. Immunosuppression use was comparable in clusters 1 and 3, but lower in cluster 2 (77.8% and 69.2% vs 11.6%, p<0.001). Rates of complete remission were greatest in clusters 1 and 3 vs cluster 2: 57.7% and 66.7% vs 37.2%. CONCLUSION: People who received immunosuppression had lower serum albumin and achieved remission more frequently, but were also prone to relapse. Our cluster analysis highlighted 3 FSGS phenotypes: a nephrotic cluster that clearly require immunosuppression; a cohort with preserved serum albumin and non-nephrotic range proteinuria who will benefit from supportive care; and lastly a cluster with heavy proteinuria but serum albumin > 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression. TRIAL REGISTRATION: This study protocol was reviewed and approved by the 'Research and Innovation committee of the Northern Care Alliance NHS Group', study approval number (Ref: ID 22HIP54).

Improving outpatient clinic experience: the future of chronic kidney disease care and associated multimorbidity.

BACKGROUND: Chronic kidney disease (CKD) is estimated to affect more than 2.5 million adults in England, and this is expected to rise to 4.2 million by 2036 (1). Population-level digital healthcare systems have the potential to enable earlier detection of CKD providing an opportunity to introduce interventions that attenuate progression and reduce the risk of end-stage kidney disease (ESKD) and cardiovascular diseases (CVD). Services that can support patients with CKD, CVD, and diabetes mellitus (DM) have the potential to reduce fragmented clinical care and optimise pharmaceutical management. METHODS AND RESULTS: The Salford renal service has established an outpatient improvement programme which aims to address these issues via two projects. Firstly, the development of a CKD dashboard that can stratify patients by their kidney failure risk equation (KFRE) risk. High-risk patients would be invited to attend an outpatient clinic if appropriate. Specialist advice and guidance would be offered to primary care providers looking after patients with medium risk. Patients with lower risk would continue with standard care via their primary care provider unless there was another indication for a nephrology referral. The CKD dashboard identified 11546 patients (4.4% of the total adult population in Salford) with T2DM and CKD. The second project is the establishment of the Metabolic CardioRenal (MRC) clinic. It provided care for 209 patients in the first 8 months of its establishment with a total of 450 patient visits. Initial analysis showed clustering of cardiorenal metabolic diseases with 85% having CKD stages 3 and 4 and 73.2% having DM. In addition, patients had a significant burden of CVD with 50.2% having hypertension and 47.8% having heart failure. CONCLUSION: There is a pressing need to create new outpatient models of care to tackle the rising epidemic of cardio-renal metabolic diseases. This model of service has potential benefits at both organisational and patient levels including improving patient management via risk stratification, increased care capacity and reduction of variation of care. Patients will benefit from earlier intervention, appropriate referral for care, reduction in CKD-related complications, and reduction in hospital visits and cardiovascular events. In addition, this combined digital and patient-facing model of care will allow rapid translation of advances in cardio-renal metabolic diseases into clinical practice.

The Role of PLA2R in Primary Membranous Nephropathy: Do We Still Need a Kidney Biopsy?

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome amongst the non-diabetic adult population. A fifth of idiopathic nephrotic syndrome cases can be attributed to MN, rising to more than 40% in older patients over 60 years. Most MN cases are classified as being of a primary cause, where there is absence of a secondary disease process explaining its manifestation. Traditionally, the standard approach of diagnosing MN involves performing a kidney biopsy as histological evaluation offers not only conclusive evidence of the diagnosis but also provides valuable information regarding disease chronicity and the presence of any other kidney histopathological features. Nevertheless, kidney biopsy is an invasive procedure which poses risks for the patient including bleeding and pain and bears greater costs for the health system. The identification of the phospholipase A2 receptor (PLA2R) antigen in 2009 was a landmark discovery, one which has evolved our understanding of the disease processes in MN and subsequently our management approach of this condition. Antibodies against PLA2R (PLA2RAb) have since emerged as an attractive non-invasive test option to be applied for the diagnosis and prognostication of primary MN. However, much debate and unknowns remain about the accuracy and reliability of testing for PLA2RAb across various primary MN scenarios. We provide a review summarizing the historical journey of PLA2R in relation to its significance in primary MN and, more importantly, evidence emerging over the years which contemplated the role of PLA2RAb as a diagnostic and prognostic tool in primary MN.

Obesity and chronic kidney disease: A current review.

Background: Obesity poses significant challenges to healthcare globally, particularly through its bi-directional relationship with co-morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods: A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings: Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity-related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion: Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi-faceted actions on major outcomes.

Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation.

INTRODUCTION: We evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors. METHODS: A retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods. RESULT: 336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9 year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

The Role of Iron in Calciphylaxis-A Current Review.

Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients. Few observational studies support the role of iron in the pathogenesis of calciphylaxis although data from the pivotal trial was not strongly supportive of this argument, i.e., no difference in incidence of calciphylaxis between the low-dose and high-dose iron treatment arms. Elevated levels of vascular cell adhesion molecules in association with iron excess were postulated to the pathogenesis of CUA by causing inflammation and calcification within the microvasculature. In-addition, oxidative stress generated because of iron deposition in cases of systemic inflammation, such as those seen in ESRD, may play a role in vascular calcification. Despite these arguments, a direct correlation between cumulative iron exposure with CUA incidence is not clearly demonstrated in the literature. Consequently, we do not have evidence to recommend iron reduction or cessation in ESRD patients that develop CUA.

A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades.

INTRODUCTION: Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. METHODS: 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. RESULTS: Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90µmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, p<0.001). The median follow-up period was 59.5 months. CONCLUSION: We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

The epidemiology and evolution of IgA nephropathy over two decades: A single centre experience.

BACKGROUND AND OBJECTIVES: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, with an incidence of 2.5 per 100,000 population per year. The 10-year risk of progression to end stage kidney disease (ESKD) or halving of eGFR is 26%. Here we aimed to collect a comprehensive dataset of IgAN patients at our centre over 2 decades to provide real world data, describe outcomes and determine the effects of immunosuppression use. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: All patients diagnosed with biopsy-proven IgAN at our centre over 2 decades were identified. After exclusions, the total cohort size was 401. Data relating to (i) baseline demographics, (ii) laboratory and urine results, (iii) histological data, and (iv) outcomes of initiation of renal replacement therapy (RRT) and mortality were collected. RESULTS: The median age was 45.0 years, with 69.6% male and 57.6% hypertensive; 20.4% received immunosuppression, 29.7% progressed to RRT and 19.7% died, over a median follow up period of 51 months. Baseline eGFR was 46.7ml/min/1.73m2 and baseline uPCR was 183mg/mmol. Median rate of eGFR decline was -1.31ml/min/1.73m2/year. Those with a higher MEST-C score had worse outcomes. Immunosuppression use was associated with an increased rate of improvement in proteinuria, but not with a reduction in RRT or mortality. Factors favouring improved outcomes with immunosuppression use included female gender; lower age, blood pressure and T-score; higher eGFR; and ACEi/ARB use. CONCLUSIONS: A variety of clinical and histological factors are important in determining risk of progression in IgAN. Therapeutic interventions, particularly use of immunosuppression, should be individualised and guided by these factors.

COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry.

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.