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Background: Cardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increas ingly diagnosed in older individuals who may have diabetes mellitus (DM). We evaluated the impact of DM on metabolic profile, renal and cardiovascular outcomes during treatment and follow-up of individuals with glomerulonephritis. Methods: We performed a retrospective cohort study of 601 consecutive adults with biopsy-proven glomerulonephritis for factors as sociated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were ex cluded. Results: The median patient age was 49.8 years (36.7-60.9 years) with estimated glomerular filtration rate of 56.7 mL/min/1.73㎡ (27.7-93.2 mL/min/1.73㎡). DM was present in 25.4%. The most frequent diagnoses were minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) (29.5%), lupus nephritis (21.3%), immunoglobulin A (IgA) nephropathy (19.1%), and mem branous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 in dividuals with lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, MCD/FSGS, membranous nephropathy, and IgA nephropathy, 52 (10.2%) developed kidney failure at a median 16.4 months (IQR, 2.3-32.2 months), while 29 (5.7%) had cardio vascular-related hospitalizations at 12.9 months (IQR, 4.8-31.8 months) and 31 (6.1%) died at 13.5 months (IQR, 2.5-42.9 months) after diagnosis. Cox regression analysis found that baseline DM was independently associated with kidney failure (adjusted hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.06-4.05, p = 0.03) and cardiovascular-related hospitalization (adjusted HR, 2.69; 95% CI, 1.21-5.98, p = 0.02) but not with mortality. Conclusion: DM was strongly associated with kidney failure and hospitalization for cardiovascular events in patients with biopsy-prov en glomerulonephritis.

Objective In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. Materials and methods This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. Results The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. Conclusion The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Individuals undergoing kidney biopsy are increasingly older and may have concurrent illnesses that cause deranged hematological and renal parameters that are associated with post-biopsy bleeding. We aimed to develop a clinical risk model to quantify bleeding risks in high-risk individuals with multiple risk factors. Single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 2 mg/dL (176 µmol/L) and had ultrasound-guided percutaneous native kidney biopsies between June 2011 and July 2015 in our tertiary referral center. The primary outcome was major bleeding, defined as need for red cell transfusion, radiological or surgical intervention, or if bleeding led to death within 7 days after kidney biopsy. Among 184 native kidney biopsies with serum creatinine ≥ 2 mg/dL, median age was 54.1 years and eGFR was 18.8 ml/min/1.73 m2. Major bleeding occurred in 19 biopsies (10.3%). Multivariate analysis accounting for age, weight, hemoglobin, platelet, prothrombin time and urea found that higher hemoglobin (adjusted OR 0.51, 95% CI 0.33–0.79, p = 0.003) and platelet (adjusted OR 0.99, 95% CI 0.98–0.99, p = 0.01) were independently associated with reduced major bleeding. A risk model that included (1) age ≥ 62 years old, (2) hemoglobin

AIM Clinical presentation and course of Immunoglobulin A nephropathy vary by ethnicity and geography and significance of extracapillary proliferation or crescents (IgAN-C) in Southeast Asia is not well described. We aimed to describe the clinical course of IgAN-C in Singapore. METHODS Retrospective cohort study of adult biopsy-proven IgAN diagnosed between February 2011 and October 2016 in 2 hospital-based nephrology units. Outcome was chronic kidney disease (CKD) progression, defined as reduction in eGFR ≥50% or end stage renal failure (ESRF). RESULTS One hundred and forty-five patients were studied. Among individuals with IgAN-C (n = 44, 30%), 38 patients had cellular or fibrocellular crescents in 1 to 25% of the glomeruli and 6 had crescents in >25%. Median eGFR was 54 (33, 83) mL/min/1.73 m2 . Compared to IgAN without crescents, IgAN-C had greater proteinuria (median 2.9 [1.4, 5.4] g/g vs 1.9 [1.1, 3.6] g/g, P = .03) and more had endocapillary hypercellularity (96% vs 39%, P

BACKGROUND Glomerulonephritis commonly causes kidney failure. Immunosuppressant treatment may be diabetogenic, but data on hyperglycaemia in glomerulonephritis treated with usual clinical care are scant. AIM To assess the epidemiology, risk factors and outcomes for new-onset diabetes among patients with glomerular disease (NODAG). METHODS A single-centre retrospective cohort of nondiabetic adults diagnosed with glomerulonephritis between January 2011 and July 2015. Clinical, laboratory and pharmacotherapy data were retrieved from electronic medical records. Using modified American Diabetes Association criteria, the primary outcome of NODAG was present if fasting venous glucose was ≥7 mmol/L for at least two readings, HbA1c was ≥6.5% or if patient required antidiabetic medications. Secondary outcomes were end-stage renal disease, cardiovascular disease and death. RESULTS NODAG occurred in 48 patients (10.7%); 22 required antidiabetic medication at median 6.2 (interquartile range 1.7, 20.0) months after glomerulonephritis diagnosis. Patients with NODAG had higher prebiopsy fasting glucose, greater proteinuria and lower fasting high-density lipoprotein cholesterol levels. Methylprednisolone and cyclophosphamide were more commonly used among patients with NODAG. In multivariate logistic regression, greater proteinuria (odds ratio 1.08 (95% confidence interval 1.01, 1.16), P = 0.02) and methylprednisolone use (odds ratio 4.02 (95% confidence interval 1.76, 9.18), P = 0.001) were significantly associated with NODAG, independent of the triglyceride/high-density lipoprotein cholesterol ratio as a surrogate measure of insulin resistance. Median follow up was 39.6 (26.9, 57.2) months. Secondary outcomes were not significantly different in patients with and without NODAG. CONCLUSION Proteinuria and methylprednisolone were associated with incident diabetes among patients with glomerular disease treated with usual care. At-risk patients should be appropriately counselled and monitored for hyperglycaemia.

Objective: The pattern of glomerulonephritis (GN) in Singapore is compared with that of 19 other countries to review changing trends in the evolution of GN in Asian, Eastern, and Western countries. Method: Three thousand two hundred and eighty-nine renal biopsies in Singapore were reviewed and compared with that of 19 other countries. Results: IgA nephritis is on the decline in many countries, including Singapore, though it still remains the commonest GN in Singapore. Membranous GN that if used to be more frequently present in Western countries has also declined though it continues a rising trend in countries such as Singapore and China. Worldwide, the frequency of focal sclerosing glomerulosclerosis (FSGS) continues to increase in many countries, but in some countries, the frequency is still low with mesangiocapillary GN remaining indigenous. Conclusion: Urbanization and socioeconomic changes and less exposure to parasitic and other infestations have transformed Singapore’s pattern, which is tending toward that of more developed countries. Antigenic exposure due to lifestyle changes, environmental, and industrial pollution are significant contributory factors that affect the evolutionary trend of GN in many countries. The rising trend in the frequency of FSGS may reflect aging and obesity.

Background and Aims Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with cardiovascular and kidney adverse effects, especially in older adults. However, NSAIDs are still frequently prescribed to some at-risk groups. We aimed to evaluate the burden of traditional cardiovascular risk factors and pattern of NSAID prescription in the very-old and young-old. Method Cross-sectional study of older adults who received prescriptions over 3 years from a large healthcare cluster in Singapore. Individuals aged 65-79 years were the “young-old” and those ≥80 years were the “very-old”. Prescriptions and traditional cardiovascular risk factors were retrieved from electronic records. Results Among 197,932 older adults (including 41,079 very-old), 49.9% received at least 1 NSAID prescription. Topical NSAIDs were more frequently prescribed among the 19,979 very-old with NSAID prescriptions (91.5% versus 82.9% of the young-old), while oral non-selective (22.1% versus 38.5%) and selective NSAID (15.1% versus 24.9%) were less frequently prescribed compared to the young-old (all p Table 1 shows that among the very-old, the odds of receiving oral non-selective NSAIDs was significantly lower in those with cardiovascular disease, while the odds of receiving oral COX II inhibitors was significantly higher in female and hypertension. Among the young-old, the odds of receiving oral non-selective NSAID was lower in those with cardiovascular disease, diabetes and chronic kidney disease, while the odds of receiving oral COX II inhibitors was higher in female, hypertension, cardiovascular disease and lower in diabetes and chronic kidney disease. Conclusion This study highlights that NSAIDs were frequently prescribed among older adults with comorbidities that may predispose to NSAID-associated adverse events. Physician education and policies are required to avoid potentially inappropriate prescriptions.

Background and Aims Population aging is an increasing phenomenon worldwide and consequently more are developing kidney diseases which may necessitate diagnostic kidney biopsy. However, older patients may be at increased risk for complications such as bleeding. We aimed to examine the utility and safety of native kidney biopsies among our older adults. Method This was a single-centre retrospective study of older adults (≥60 years) who had native kidney biopsies at the Singapore General Hospital between June 2011 and March 2015. Demographic data, co-morbid illnesses, clinical presentation at kidney biopsy, as well as laboratory results before and after kidney biopsy, were retrieved from electronic medical records. Patient outcomes were recorded until their last visit or death before 30th March 2017. End stage renal disease (ESRD) was defined as estimated glomerular filtration rate (eGFR) 3 months. All post biopsy bleeding events were documented, with major bleeding defined as the need for transfusion and/or intervention; or if bleeding was either a direct or contributory cause of death. Results Older adults accounted for 153 of 545 (28.1%) native renal biopsies performed. The indications for biopsy in older adults included microscopic hematuria with proteinuria (51.0%), nephrotic syndrome (32.0%) and isolated proteinuria (17.0%). One hundred and ten patients (71.9%) had eGFR Post biopsy, major bleeding was more frequent among older adults compared with younger adults (13.3% vs 5.7% respectively; p=0.04), although overall bleeding episodes between older and younger adults were not significantly different (15.9% vs 22.9% respectively; p=0.18). Among older adults, minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) was the most frequent diagnosis (23.5%), followed by membranous nephropathy (20.9%) and IgA nephropathy (9.8%), whereas MCD/FSGS (26.5%), lupus nephritis (24.5%) and IgA nephropathy (19.6%) were the top three diagnoses amongst younger adults. Co-existing glomerulonephritis (GN) with diabetic nephropathy and isolated diabetic nephropathy were seen in 12 (7.8%) and 20 (13.1%) elderly patients respectively. The majority (124 patients, 81.0%) of biopsies in older adults had histological diagnoses of glomerulonephritis that were potentially amendable to treatment although only 90 (58.8%) patients subsequently received immunosuppressants. Among older adults with biopsy-proven glomerulonephritis, median follow up was similar between those treated and not treated with immunosuppressants (30.4 [27.3, 53.7] months versus 38.8 [30.7, 51.9] months, p=0.12). Among older adults with GN, ESRD was less frequent among those treated with immunosuppressants, compared to those who did not receive immunosuppressants, although the difference did not reach statistical significance (10.3% versus 18.9%, p=0.24). However, the combined endpoint of ESRD or mortality were similar (24.1% vs 21.6%, p=0.76). Conclusion Our findings support the utility of renal biopsy for diagnosis and to guide clinical care. Older adults undergoing kidney biopsy should be counselled and monitored for bleeding complications.

Background and Aims Phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN) and the detection of circulating autoantibodies to PLA2R (Anti-PLA2R Ab) is a major advance in understanding this disease. In this study, we aimed to determine if Anti-PLA2R Ab serves as a specific marker for PMN in our multi-ethnic Southeast Asian cohort. Method This was a prospective cohort study of all adults with glomerular disease undergoing biopsy between 1st January 2015 and 30th June 2018. Anti-PLA2R antibody levels were quantitatively determined by IgG ELISA (Euroimmun). Results are expressed as RU/ml. We considered a value of >20RU/ml to represent a positive result, value of Results Out of the cohort of 192 patients, there were 27 patients with Membranous Nephropathy (MN), with 12 PMN and 15 with secondary MN (SMN). Secondary causes were Hepatitis (1), Malignancy (1), Lupus (13). In our analyses, 10 (83.3%) PMN pts were positive for Anti-PLA2R Ab, with 7(58.3%) strongly positive with titres >200RU/ml and 2(16.7%) negative. For SMN, the majority, 12 out of 14 patients (85.7%) tested negative and the remaining 2 (7.7%) yielded values of indeterminate levels. Of note, among the 165 patients with non membranous glomerular disease, there were 15 patients (9.1%) with indeterminate Anti-PLA2R Ab levels and 31 patients (18.9%) tested positive for Anti-PLA2R antibody, with levels >20 RU/ml. Of these 31 patients, the majority of the patients had low levels of Anti-PLA2R Ab of 50 RU/ml and their characteristics are tabled below (Table 1) Conclusion Consistent with other published studies, positive Anti-PLA2R antibody levels were highly specific for PMN in our multi-ethnic Southeast Asian population and our centre has since been consistently using this test for differentiating between PMN and SMN. What is most striking in our study is that we have found high-titre Anti-PLA2R antibody positivity in non-MN patients, which has not been frequently reported in literature. The unifying feature amongst these patients appear to be the presence of arterial and arteriolar sclerosis which is usually non-specific. Though we would not normally do the Anti-PLA2R antibody test in a patient with low suspicion of MN, our study findings warrants further investigation and may indicate the limited usefulness of Anti-PLA2R antibody levels as a screening tool for glomerulonephritis.

Background and Aims Nephrotic syndrome is associated with hypercholesterolemia, while its treatment, often involving high-dose glucocorticosteroids, may cause hyperglycemia. Proprotein convertase subtilisin /kexin type 9 (PCSK9) regulates plasma cholesterol and is associated with post-transplant diabetes. Although a potential therapeutic target in nephrotic syndrome, the relationships between PCSK9 and lipid parameters are not well established. We aimed to characterize serum PCSK9 and metabolic parameters among individuals with nephrotic syndrome. Method Single-center prospective cohort study of non-diabetic adults newly-diagnosed with nephrotic syndrome and subsequently treated with immunosuppressant. Fasting serum PCSK9 was measured using ELISA at diagnosis. Clinical history, blood pressure, body mass index (BMI), waist-to-hip ratio (WHR) and biochemistry (fasting glucose and lipid, HbA1c and fasting serum PCSK9) were obtained at diagnosis and at 3 months during immunosuppression therapy. Spearman’s correlation was used to evaluate for associations between PCSK9 and glycemic and lipid parameters. Results Among 15 adults with nephrotic syndrome, the majority was female (60%) and Chinese (80%). Median age was 40 (IQR 26, 51) years. The most frequent diagnoses were minimal change disease or focal segmental nephrosclerosis (n=7) and lupus nephritis (n=5); the minority had IgA nephropathy, membranous nephropathy or vasculitis. At diagnosis, median eGFR was 97.9 (59.5, 120.9) ml/min/1.73 m2, UPCR 7.6 (6.1, 10.4) g/g, LDL-cholesterol 4.6 (3.1, 6.7) mmol/L and fasting serum PCSK9 317.6 (276.8, 470.1) ng/ml. PCSK9 correlated positively with hypertriglyceridemia (r=0.55, p=0.03) at baseline. Most patients (n=14, 93%) were treated with prednisolone (monotherapy or in combination with other immunosuppressant) and 1 received tacrolimus monotherapy. At 3 months, the majority (n= 11, 73%) had achieved clinical remission. Fasting serum PCSK9 was higher at 3 months [median 430.6 (283.1, 496.0) ng/ml] compared to baseline, although the difference was not statistically significant. At 3 months, PCSK9 correlated positively with age (r=0.58, p=0.03), LDL-cholesterol (r=0.90, p=0.04) and change in BMI (r=0.72, p=0.01). Conclusion PCSK9 is associated with metabolic parameters at diagnosis and during the treatment course in patients with nephrotic syndrome treated with immunosuppressant.

Objective: This study on the prevalence of diabetic nephropathy (DN) and coexistence of non-diabetic renal disease (NDRD) in a cohort of 255 non-insulin-dependent diabetes mellitus (NIDDM) patients aims to determine the value of performing renal biopsies in these patients and elucidate the factors which could affect their progression to end-stage renal disease (ESRD). Methods: Among 255 NIDDM patients, 93 had DN alone, 69 had NDRD alone, and the remaining 93 had DN plus NDRD (mixed group). The indications for renal biopsy were based on clinical suspicion of superimposed NDRD, including heavy or rapidly increasing proteinuria, renal impairment even though diabetes is of relatively short duration, rapidly declining renal function, and presence of hematuria with dysmorphic red blood cells suggesting presence of glomerulonephritis. Results: The following were predictors of ESRD: high systolic BP at biopsy, longer duration of diabetes, heavy proteinuria, and presence of diabetic retinopathy. Comparing patients in the NDRD group with the DN group and the mixed group, the NDRD group had lower serum creatinine and higher eGFR with lower urinary proteinuria and higher serum albumin at presentation and on follow-up. Kimmelstiel-Wilson nodules were associated with a poorer prognosis leading to a higher occurrence of ESRD among patients with DN. Conclusion: Renal biopsy is of value in indicating the prognosis of NIDDM patients with DN based on the diabetic lesions. For NIDDM patients with atypical course and suspicion of associated NDRD, a renal biopsy would enable us to diagnose the underlying NDRD and offer appropriate therapy. Most nephrologists would consider renal biopsy for an NIDDM patient based on clinical indications like atypical clinical course and suspicion of an associated NDRD, but they would not perform a routine renal biopsy like for a CKD patient, unless it is for a research indication.

Background : Glomerulonephritis is often treated with kidney-saving, but potentially diabetogenic immunosuppressants such as glucocorticosteroids and calcineurin inhibitors. Unfortunately, there are little data on dysglycemia before and after diagnosis and during treatment of glomerulonephritis. We aimed to evaluate the occurrence and risk factors for pre-diabetes and incident diabetes among non-diabetic patients with glomerular disease with or without treatment with immunosuppressants. Methods : A single-center, retrospective cohort study was performed on 229 non-diabetic immunosuppressantnaïve adults diagnosed with glomerulonephritis and renal vasculitis. Patients with known diabetes and prior immunosuppressant treatment were excluded. Outcomes of new-onset pre-diabetes and new-onset diabetes were defined according to American Diabetic Association criteria. Results : Pre-diabetes was present pre-biopsy in 74 of the 229 patients (32.3%). During the median follow-up of 34.0 (23.3-47.5) months, 29 patients (12.7%) developed new-onset diabetes and 58 (25.3%) had new-onset prediabetes. Immunosuppressive therapy in patients with pre-existing pre-diabetes was associated with increased odds of new-onset diabetes compared to those without either risk factor (26.0% versus 5.0%; odds ratio, 6.67; 95% confidence interval [CI], 1.41 to 31.64), P = 0.02). Conclusion : New-onset diabetes after immunosuppressant treatment occurred in one-quarter of patients with glomerulonephritis and pre-existing pre-diabetes. Physicians should screen for pre-diabetes when planning treatment with immunosuppressants, as its presence significantly increases the risk of diabetes mellitus.

Background Kidney biopsy is the gold standard for diagnosing kidney disease but may result in bleeding, especially in uraemia. DDAVP (1-deamino-8-d-arginine vasopressin) may reduce uraemic bleeding but guidelines on its use are lacking. Aim To evaluate whether DDAVP reduced bleeding complications after percutaneous kidney biopsies. Methods We searched CENTRAL, PubMed, Embase, LILACS, WHO Trials Registry and ClinicalTrials.gov until May 2019 for randomised controlled trials (RCT), quasi-RCT and prospective cohort studies that compared DDAVP with placebo or no intervention, prior to native or allograft kidney biopsy. The primary outcome was post-biopsy bleeding. Secondary outcome was adverse events related to DDAVP. Results Abstracts of 270 identified papers were examined and 24 selected for evaluation. Two studies, one RCT and one prospective cohort that collectively evaluated 738 native kidney biopsies, met the inclusion criteria. One enrolled individuals with serum creatinine ≤1.5 mg/dL (132 μmol/L) and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 while the other evaluated biopsies with serum creatinine >150 μmol/L. DDAVP was administered as a single subcutaneous dose of 0.3 μg/kg in both studies. Data were not pooled for meta-analysis due to clinical heterogeneity. GRADE quality of evidence from these two studies was low for DDAVP preventing any bleeding complication after native kidney biopsy. Low quality evidence suggested that adverse effects were not increased in DDAVP therapy. No prospective studies evaluated DDAVP in transplant kidney biopsies. Conclusion Currently available prospective data are insufficient to support the routine use of DDAVP prior to percutaneous kidney biopsies hence high quality trials are required.

Background Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities. Aim To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis. Methods This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline. Results We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) μmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 m2 , P = 0.03) and higher chronicity index (5 (3-6) vs 3 (2-3), P = 0.04) than those who did not. Remission, early remission within 6 months, complete remission and non-relapse were less frequently associated with progressive CKD (P Conclusion Multi-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

Background Cytomegalovirus (CMV) infections are associated with morbidity and mortality. We aimed to describe the epidemiology, risk factors and outcomes of CMV infection among patients with glomerulonephritis (GN) who received potent immunosuppressants (IS). Methods Single-centre retrospective study of adults with biopsy-proven GN prescribed methylprednisolone (MP), cyclophosphamide (CYC) or rituximab (RTX). Primary endpoint was CMV infection defined by significant CMV antigenemia (>10 positive cells in 106 cells) or viremia (>2000 copies/ml). Death was related to CMV if CMV infection occurred within the same hospitalisation as death. Results Ninety-four patients were studied. CYC was prescribed in 65% and MP in 71% of the cohort. Only 2 patients received RTX and 15 patients received plasma exchanges (PEX). Median follow up was 31.9 (IQR: 13.7, 53.6) months. CMV infection occurred in 13 patients (13.8%) at 1.3 (0.6, 3.0) months from biopsy. Patients with CMV infection had higher serum creatinine [404 (272, 619) vs. 159 (93, 317) µmol/L, p

The anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular-renal complications, will place a significant burden on patients, caregivers, and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps, especially in Asian patients with young-onset diabetes and chronic kidney disease (CKD). Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity. These recommendations replaced the previous strategy of using low-density lipoprotein cholesterol targets to guide initiation and intensification of lipid lowering, albeit still widely practiced in Asia. The latest guidelines also highlight the high risk of atherosclerosis and cardiovascular disease (ASCVD) for people with diabetes, who should be protected with statins, except for young patients without other risk factors, who will need yearly monitoring of blood lipid levels. Given the propensity of Asian patients with diabetes to develop CKD and the amplifying effect of CKD on ASCVD, the use of statins in Asian patients is particularly important. Due to interethnic differences in drug metabolism, rosuvastatin, which is largely cleared by the kidney, should be prescribed in low dosages (5-10 mg daily) in Asian populations. Conversely, epidemiological and experimental data confirm pleotropic and organ-protective effects of atorvastatin, with proven safety in Asian populations within a daily dose range of 10-40 mg. Thus, there is a need for Asian countries to review and align their lipid-lowering treatment guidelines to reduce the substantial burden of diabetes in the Asian region.

Aim Lupus nephritis (LN) is associated with significant morbidity and mortality and hence usually treated aggressively with immunosuppressants. This predisposes LN patients to increased infections, yet few studies have evaluated LN patients for infective complications. We aimed to describe the epidemiology and identify risk factors for infections requiring hospitalisation among patients with biopsy-proven LN. Methods This was a single-centre retrospective cohort study of patients with biopsy-proven LN between 1st January 2000 and 31st May 2009. Patients were excluded if they were

Aim: Cytomegalovirus (CMV) reactivation and disease in immunocompromised individuals is associated with significant morbidity and mortality. Preventive measures such as anti-viral prophylaxis or surveillance and pre-emptive therapy effectively reduced CMV disease in solid organ transplant but have not been evaluated among patients with glomerulonephritis at-risk for CMV disease after immunosuppressive therapy. We evaluated the utility and outcomes of a risk-stratified approach to anti-viral prophylaxis for adults with glomerulonephritis treated with potent immunosuppressants. Methods: Single-center retrospective cohort study of adults with glomerulonephritis and renal vasculitis prescribed methylprednisolone, cyclophosphamide or rituximab in a tertiary referral centre. A risk-stratified approach to CMV anti-viral prophylaxis was implemented in March 2015. We compared the incidence of CMV disease in the pre-implementation (January 2008-December 2014) and post-implementation (June 2015-June 2017) groups. Results: We studied 119 individuals: 85 in the pre-implementation group and 34 in the post-implementation group. The post-implementation group had worse kidney function, greater proteinuria, higher prednisolone dose and more received intravenous methylprednisolone and plasma exchanges but CMV disease within 6 months was similar to the pre-implementation group (2.9% vs. 3.5%, p = 1.00). Among individuals in the post-implementation group who satisfied criteria to receive anti-viral prophylaxis (n = 21), CMV disease was more frequent in the group not given prophylaxis compared to those given prophylaxis as recommended (8.3% versus 0%, p = 1.00). Adverse events related to anti-viral prophylaxis occurred in 40%. Conclusion: This study provided pilot data for future randomized controlled trials to evaluate CMV preventive strategies in selected high-risk patients with glomerulonephritis or renal vasculitis.

This review of 3,289 native kidney biopsies over the past four decades in Singapore documents the changing pattern of biopsy-proven glomerulonephritis (GN)from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative GN was the most common form of primary GN, similar to the Asian region. In the 2nd decade, the percentage of mesangial proliferative GN decreased, but membranous GN became more common, as was seen in China and Thailand. In the 3rd decade, focal segmental glomerulosclerosis (FSGS) and membranous nephropathy continued to rise, but it was only recently, in the 4th decade, that FSGS prevalence increased dramatically, although membranous nephropathy continues to increase in some Asian countries. In the last decade in Singapore, Malaysia, and Japan, prevalence of IgA nephritis has decreased but remains the most common GN. The percentage of FSGS continues to increase in many countries like in Italy, United States of America, United Kingdom, China, and Malaysia. We surmise that socioeconomic factors play significant roles in the evolution of the renal biopsy pattern. .

Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment. This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding. 240 native kidney and 196 allograft biopsies were performed. Median age was 51 (IQR 42.3, 60) years and eGFR was 21.9 (12.9, 30.1) ml/min/1.73 m2. Although patients prescribed desmopressin prophylaxis (n = 226) had higher serum creatinine [279 (201, 392) vs. 187 (160, 241), p

BackgroundThere are limited studies documenting infection epidemiology in lupus nephritis (LN) patients. We aimed to study infection incidences and risk characteristics and ascertain possible predictors of infective outcomes in a multiethnic Asian population.MethodsThis retrospective study from 2006 to 2012 included newly diagnosed LN patients. We collected admissions, immunosuppression, and infection data until end-stage renal failure, death, last follow-up, or the year 2015. The infection incidence rates were evaluated and a generalized linear latent and mixed models (GLLAMM) analysis was carried out to evaluate potential predictors of infection.ResultsOur cohort of 101 patients consisted of mainly Chinese (75.2%), females (78.2%), and a median age of 38 years (IQR 26–49). The median time of follow-up was 72.8 months (IQR 49.5–94.0). Six out of 14 patient deaths were infection related. Seventy-eight out of 200 admissions, with a total of 102 episodes of infection, occurred in 46 patients. The incidence of infection rates leading to admissions was 10.3 per 100 person-years and the incidence of infection episodes rates was 17.6 per 100 person-years. Cytomegalovirus (CMV) was the most common organism identified. Univariate GLLAMM analysis showed Malay compared to Chinese ethnicity (HR 2.833 (95% CI 1.088–7.373)), use of oral cyclophosphamide (HR 6.618 (95% CI 1.015–43.154)) and rituximab (HR 3.967 (95% CI 1.157–13.603)) as predictors of infection-related admissions. Malay ethnicity and rituximab remained significant in the multivariate GLLAMM analysis.ConclusionsOur study highlights substantial infection incidences in patients with LN and its contribution to deaths.

Glomerulonephritis commonly causes kidney failure. Immunosuppressant treatment may be diabetogenic, but data on hyperglycaemia in glomerulonephritis treated with usual clinical care are scant.To assess the epidemiology, risk factors and outcomes for new-onset diabetes among patients with glomerular disease (NODAG).A single-centre retrospective cohort of nondiabetic adults diagnosed with glomerulonephritis between January 2011 and July 2015. Clinical, laboratory and pharmacotherapy data were retrieved from electronic medical records. Using modified American Diabetes Association criteria, the primary outcome of NODAG was present if fasting venous glucose was ≥7 mmol/L for at least two readings, HbA1c was ≥6.5% or if patient required antidiabetic medications. Secondary outcomes were end-stage renal disease, cardiovascular disease and death.NODAG occurred in 48 patients (10.7%); 22 required antidiabetic medication at median 6.2 (interquartile range 1.7, 20.0) months after glomerulonephritis diagnosis. Patients with NODAG had higher prebiopsy fasting glucose, greater proteinuria and lower fasting high-density lipoprotein cholesterol levels. Methylprednisolone and cyclophosphamide were more commonly used among patients with NODAG. In multivariate logistic regression, greater proteinuria (odds ratio 1.08 (95% confidence interval 1.01, 1.16), P = 0.02) and methylprednisolone use (odds ratio 4.02 (95% confidence interval 1.76, 9.18), P = 0.001) were significantly associated with NODAG, independent of the triglyceride/high-density lipoprotein cholesterol ratio as a surrogate measure of insulin resistance. Median follow up was 39.6 (26.9, 57.2) months. Secondary outcomes were not significantly different in patients with and without NODAG.Proteinuria and methylprednisolone were associated with incident diabetes among patients with glomerular disease treated with usual care. At-risk patients should be appropriately counselled and monitored for hyperglycaemia.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mercredi 7 mars 2018

Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities.To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis.This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline.We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) μmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 mMulti-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

Aim: Few studies have evaluated patients after cardiac surgery for subsequent chronic kidney disease (CKD) which increases cardiovascular morbidity and mortality. This study aimed to ascertain the long-term renal outcome in adult patients with severe acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery. Methods: This is a single-center retrospective cohort study of consecutive adult patients who received acute dialysis for AKI after CABG between February 8, 2009 and January 30, 2011. Data on pre- and intra-operative factors were retrieved from electronic medical records. The primary endpoint was CKD progression as defined by dialysis dependence or doubling of serum creatinine from the pre-operative level. Secondary endpoints included in-hospital mortality and renal function at 3 months and 1 year. Results: Fifty-five patients required acute dialysis after CABG. The median age was 67 years (IQR: 61, 75), and 70.9% were male. Median pre-operative serum creatinine was 157 µmol/l (IQR: 122, 203). A total of 19 patients (34.5%) died. The median follow-up time for hospital survivors was 44.2 months (IQR: 25.0, 49.4) after surgery. Among the 36 survivors, 14 patients (38.9%) reached the primary endpoint. Patients with CKD progression had higher pre-operative serum creatinine [median 214 µmol/l (IQR: 159, 399) vs. 155 µmol/l (112, 187), p = 0.015] and lower eGFR [median 20.4 ml/min/1.73 m2 (IQR: 11.9, 38.2) vs. 39.9 ml/min/1.73 m2 (25.9, 55.5), p = 0.027] compared to those who did not have CKD progression. Conclusion: Patients with severe AKI after CABG are at high risk of long-term renal dysfunction and should be monitored regularly for deterioration.

The anticipated increase in the prevalence and incidence of type 2 diabetes in Asia, and its associated cardiovascular-renal complications, will place a significant burden on patients, caregivers, and society. Despite the proven effectiveness of lipid management in reducing these complications, there are major treatment gaps, especially in Asian patients with young-onset diabetes and chronic kidney disease (CKD). Recent international guidelines recommended the adoption of absolute risk estimation of atherosclerosis and cardiovascular disease to guide treatment intensity. These recommendations replaced the previous strategy of using low-density lipoprotein cholesterol targets to guide initiation and intensification of lipid lowering, albeit still widely practiced in Asia. The latest guidelines also highlight the high risk of atherosclerosis and cardiovascular disease (ASCVD) for people with diabetes, who should be protected with statins, except for young patients without other risk factors, who will need yearly monitoring of blood lipid levels. Given the propensity of Asian patients with diabetes to develop CKD and the amplifying effect of CKD on ASCVD, the use of statins in Asian patients is particularly important. Due to interethnic differences in drug metabolism, rosuvastatin, which is largely cleared by the kidney, should be prescribed in low dosages (5-10 mg daily) in Asian populations. Conversely, epidemiological and experimental data confirm pleotropic and organ-protective effects of atorvastatin, with proven safety in Asian populations within a daily dose range of 10-40 mg. Thus, there is a need for Asian countries to review and align their lipid-lowering treatment guidelines to reduce the substantial burden of diabetes in the Asian region.

Gastrointestinal cytomegalovirus (CMV) disease in ANCA-associated vasculitis is associated with significant morbidity. Studies should be performed to identify the epidemiology and risk factors for CMV disease in AAV so that vulnerable patients may be risk-stratified for consideration of preventive strategies such as surveillance and pre-emptive therapy or anti-viral prophylaxis. Given the absence of evidence-based guidelines for prevention of CMV disease in patients with AAV receiving potent immunosuppressive therapy, further risk-benefit studies are required to ascertain if preventive strategies will reduce CMV-related morbidity and mortality in individuals with AAV.

BACKGROUND In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p

Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies. .

Background: This is a comparative study of a 6 year retrospective analysis of the therapeutic efficacy and safety of Combined Aliskiren (150 mg a day) and Losartan (100 mg a day) in a Clinical Trial setting versus a Usual Care group of patients on Losartan (100 mg a day), Telmisartan (80 mg a day) and Combined Enalapril (10 mg a day) plus Losartan (100mg a day) in non-Diabetic Chronic Kidney Disease (CKD) patients. The objective of this study was to ascertain if there were any differences in the renal outcome of patients treated within a Clinical Trial setting versus a Usual Care setting. The study seeks to establish the relevance of having a Usual Care group as a comparator and whether its inclusion in the study would help to validate the findings in the Clinical Trial groupMethods: This is a 2nd Phase follow up study three years after the initial 1st Phase study in the Clinical Trial Group. Patients in the 2nd Phase study were those who continued to have proteinuria and were treated with Losartan 100mg a day. The 2nd Phase study seeks to document the incidence of remission of proteinuria following their initial 1st Phase therapy for proteinuria compared to those in the Usual Care group where treatment remained unchanged from year 1 to end of year 6. The rates of remission of proteinuria and improvement of renal function as well as associated comorbidities between the 2 groups are compared.Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (pConclusions: This study shows that patients in a Clinical Trial setting do better than those in the Usual Care setting as they are more likely to have improvement in renal function with remission of proteinuria.