Desmopressin acetate to prevent bleeding in percutaneous kidney biopsy: a systematic review.

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.

Clinical course of Immunoglobulin A nephropathy with crescents in a multi-ethnic Southeast Asian cohort.

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 < .001). IgAN-C were also more likely to receive immunosuppressants (66% vs 43%, P = .01) such as prednisolone (63% vs 38%, P = .006) and cyclophosphamide (12% vs 2%, P = .03). Median follow up was 27 (12, 46) months. IgAN-C were more likely to achieve proteinuria reduction ≥50% at 6 months (66% vs 44%, P = .03). CKD progression within 12 months was not different among those with and without crescents (13% vs 10% respectively, P = .73). However, immunosuppressant treatment of IgAN-C was associated with reduced ESRF (0 vs 20%, P = .03). CONCLUSION: Immunosuppressants may attenuate the risk of ESRF in IgAN-C.

New-onset diabetes mellitus among patients with glomerular diseases.

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.

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study.

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 < 0.01). 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.

Epidemiology and risk factors for cytomegalovirus infection in glomerular diseases treated with immunosuppressive therapy.

AIM: 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 antigenaemia (>10 positive cells in 106 cells) or viraemia (>2000 copies/mL). Death was related to CMV if CMV infection occurred within the same hospitalization as death. RESULTS: Ninety-four patients were studied. CYC was prescribed in 65% and MP in 71% of the cohort. Only two 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 < 0.001] and greater proteinuria [UPCR 7.5, (4.8, 11.8) vs. 4.2 (2.3, 8.4) g/g, P = 0.02] than those who did not have CMV infection. Also, more patients received CYC (92% vs. 60%, P = 0.03), RTX (15% vs. 0, P = 0.02) and PEX (38% vs. 12%, P = 0.01) than those who did not have CMV infection. Two patients had CMV-related deaths. CONCLUSION: Cytomegalovirus infection is common in GN patients receiving potent IS. Surveillance and possibly anti-viral prophylaxis should be considered for high-risk patients.

Severe infections in patients with lupus nephritis treated with immunosuppressants: A retrospective cohort study.

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 hospitalization among patients with biopsy-proven LN. METHODS: This was a single-centre retrospective cohort study of patients with biopsy-proven LN between 1 January 2000 and 31 May 2009. Patients were excluded if they were <16 years old at time of biopsy, had previous kidney transplant or if pharmacotherapy data were incomplete. Hospitalizations for infections, bacteraemia and polymicrobial infections were recorded until patients' last visit or when they received immunosuppression for non-glomerulonephritis indications, such as solid organ transplant or chemotherapy. RESULTS: We studied 189 patients who had biopsy-proven lupus nephritis. Median age at diagnosis was 36.9 (IQR: 27.4, 47.5) years and 82% were female. Most patients received at least one immunosuppressant after LN diagnosis, including glucocorticosteroids in 94.2%. One hundred and four patients (60.3%) had at least one hospitalization for infection at 11 (1, 53) months from diagnosis. Bacteraemia occurred in 26 patients (13.8%) and 32 patients (16.9%) had polymicrobial infections. On multivariate analysis, LN relapse was associated with hospitalization for infection (OR 2.33 (1.18, 4.60), P = 0.01) and bacteraemia (OR 3.47 (1.05, 11.45), P = 0.04). Infection-related mortality occurred in 10 patients (5.3%). CONCLUSION: Serious infections are common among patients with LN and are associated with mortality.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
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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 < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
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Early repeat hospitalization for fluid overload in individuals with cardiovascular disease and risks: a retrospective cohort study.

AIMS: Fluid overload is a common manifestation of cardiovascular and kidney disease and a leading cause of hospitalizations. To identify patients at risk of recurrent severe fluid overload, we evaluated the incidence and risk factors associated with early repeat hospitalization for fluid overload among individuals with cardiovascular disease and risks. METHODS: Single-center retrospective cohort study of 3423 consecutive adults with an index hospitalization for fluid overload between January 2015 and December 2017 and had cardiovascular risks (older age, diabetes mellitus, hypertension, dyslipidemia, kidney disease, known cardiovascular disease), but excluded if lost to follow-up or eGFR < 15 ml/min/1.73 m2. The outcome was early repeat hospitalization for fluid overload within 30 days of discharge. RESULTS: The mean age was 73.9 ± 11.6 years and eGFR was 54.1 ± 24.6 ml/min/1.73 m2 at index hospitalization. Early repeat hospitalization for fluid overload occurred in 291 patients (8.5%). After adjusting for demographics, comorbidities, clinical parameters during index hospitalization and medications at discharge, cardiovascular disease (adjusted odds ratio, OR 1.66, 95% CI 1.27-2.17), prior hospitalization for fluid overload within 3 months (OR 2.52, 95% CI 1.17-5.44), prior hospitalization for any cause in within 6 months (OR 1.33, 95% CI 1.02-1.73) and intravenous furosemide use (OR 1.58, 95% CI 1.10-2.28) were associated with early repeat hospitalization for fluid overload. Higher systolic BP on admission (OR 0.992, 95% 0.986-0.998) and diuretic at discharge (OR 0.50, 95% CI 0.26-0.98) reduced early hospitalization for fluid overload. CONCLUSION: Patients at-risk of early repeat hospitalization for fluid overload may be identified using these risk factors for targeted interventions.

Hospital readmissions for fluid overload among individuals with diabetes and diabetic kidney disease: risk factors and multivariable prediction models.

AIMS: Hospital readmissions due to recurrent fluid overload in diabetes and diabetic kidney disease can be avoided with evidence-based interventions. We aimed to identify at-risk patients who can benefit by developing risk prediction models for readmissions for fluid overload in people living with diabetes. METHODS: Single-center retrospective cohort study of 1531 adults with diabetes and hospitalized for fluid overload, including congestive heart failure, pulmonary edema and generalized edema, between 2015 and 2017. The multivariable regression models for 30-day and 90-day readmission for fluid overload were compared with the LACE score for discrimination, calibration, sensitivity, specificity and net reclassification index (NRI). RESULTS: Readmissions for fluid overload within 30 days and 90 days occurred in 8.6% and 17.2% of patients with diabetes, and 8.2% and 18.3% of patients with diabetic kidney disease, respectively. After adjusting for demographics, comorbidities, clinical parameters, and medications, a history of alcoholism (HR 3.85, 95% CI 1.41-10.55) and prior hospitalization for fluid overload (HR 2.50, 95% CI 1.26- 4.96) were independently associated with 30-day readmission in patients with diabetic kidney disease, as well as in individuals with diabetes. Additionally, current smoking, absence of hypertension and high-dose intravenous furosemide were also associated with 30-day readmission in individuals with diabetes. Prior hospitalization for fluid overload (HR 2.43, 95% CI 1.50-3.94), cardiovascular disease (HR 1.44, 95% CI 1.03-2.02), eGFR ≤45 ml/min/1.73 m2 (HR 1.39, 95% CI 1.003-1.93) were independently associated with 90-day readmissions in individuals with diabetic kidney disease. Additionally, thiazide at discharge reduced 90-day readmission in diabetic kidney disease while high-dose intravenous furosemide predicted 90-day readmission in diabetes. The clinical and clinico-psychological models for 90-day readmission in individuals with diabetes and diabetic kidney disease had better discrimination and calibration than the LACE score. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetes were 22.4% and 28.9%, respectively. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetic kidney disease were 5.6% and 38.9%, respectively. CONCLUSION: The risk models can potentially be used to identify patients at-risk of readmission for fluid overload for evidence-based interventions such as patient education or transitional care programs to reduce preventable hospitalizations. .

Estimation of risk for major bleeding in native kidney biopsies in patients with multiple risk factors.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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 < 10 g/dL and (3) platelets ≤ 216 × 109/L as categorical variables predicted major bleeding post-biopsy. CONCLUSION: We developed a risk model that included multiple risk factors to quantify bleeding risks in native kidney biopsies with renal impairment.

Changes in metabolic parameters and adverse kidney and cardiovascular events during glomerulonephritis and renal vasculitis treatment in patients with and without diabetes mellitus.

BACKGROUND: Cardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increasingly 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 associated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were excluded. 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 m2 (27.7-93.2 mL/min/1.73 m2). 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 membranous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 individuals 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 cardiovascular-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-proven glomerulonephritis.

Bleeding Complications and Adverse Events After Desmopressin Acetate for Percutaneous Renal Transplant Biopsy.

INTRODUCTION: Percutaneous renal biopsy remains critical for the workup of renal allograft dysfunction but is associated with the risk of bleeding. Prophylactic intravenous desmopressin has been proposed to reduce bleeding risk in native renal biopsies, but its efficacy in the renal transplant population is unclear and adverse events such as severe hyponatraemia have been reported. MATERIALS AND METHODS: We conducted a single-centre retrospective cohort study involving adult (≥21 years old) renal transplant recipients with impaired renal function (serum creatinine ≥150 µmol/L) who underwent ultrasound-guided renal allograft biopsies from 2011‒2015 to investigate the effect of prebiopsy desmopressin on the risk of bleeding and adverse events. RESULTS: Desmopressin was administered to 98 of 195 cases who had lower renal function, lower haemoglobin and more diuretic use. Postbiopsy bleeding was not significantly different between the 2 groups (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.26‒2.43, P = 0.68) but desmopressin increased the risk of postbiopsy hyponatraemia (sodium [Na] <135 mmol/L) (adjusted OR 2.24, 95% CI 1.10‒4.59, P = 0.03). Seven cases of severe hyponatraemia (Na <125 mmol/L) developed in the desmopressin group, while none did in the non-desmopressin group. Amongst those who received desmopressin, risk of hyponatraemia was lower (OR 0.26, 95% CI 0.09‒0.72, P = 0.01) if fluid intake was <1 L on the day of biopsy. CONCLUSION: Prophylactic desmopressin for renal allograft biopsy may be associated with significant hyponatraemia but its effect on bleeding risk is unclear. Fluid restriction (where feasible) should be recommended when desmopressin is used during renal allograft biopsy. A randomised controlled trial is needed to clarify these outcomes.