Risk of Relapse of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids.

OBJECTIVE: Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. METHODS: We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time-to-event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. RESULTS: Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4-12.1) relapses per 100 patient-years. Neither the use of PLEX (subhazard ratio 0.91-0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93-0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3-ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. CONCLUSION: In patients with severe ANCA-associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk.

Participant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants' expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant's needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.

Sex and Gender Disparities in Living Kidney Donation: A Scoping Review.

Background: Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD). Methods: A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023. Results: Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%-65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD. Conclusions: Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.

Fibrillary and immunotactoid glomerulopathies in the Hunter region: a retrospective cohort study.

BACKGROUND: Fibrillary (FGN) and immunotactoid (IT) glomerulonephritis are uncommon. AIMS: To evaluate the prevalence, clinicopathological correlations and outcomes of FGN and IT in our regional centre in Australia. METHODS: We interrogated a renal biopsy database for cases of FGN and IT from 2000 to 2020. Data included demographics, serum creatinine, haematuria status, proteinuria, comorbidities and histopathological findings. RESULTS: We had 14 cases of FGN and t of IT. The mean presenting age was 59.8 years, and 42.9% were males. No patients with FGN had dysproteinaemia, whereas both patients with IT had chronic lymphocytic leukaemia. At presentation, 75% of patients with FGN and both patients with IT had haematuria; all had proteinuria. Mean albumin-creatinine ratio at presentation was 254 mg/mmol for FGN and 604 mg/mmol for IT. Mean presenting serum creatinine was 149 µmol/L for FGN and 95 µmol/L for IT. Four patients with FGN (28.6%) received immunomodulatory therapy. The prognosis of FGN was poor, with six patients (46.2%) reaching end-stage kidney disease after a median of 42 months (range 1-96 months). All patients presenting with proteinuria <30 mg/mmol entered complete remission; patients with higher-grade proteinuria exhibited progressive chronic kidney disease. Patients with IT had complete remission with treatment of underlying haematological disease. CONCLUSION: FGN is rare, with poor response to immunomodulatory therapy. It carries poor renal prognosis. Less proteinuria at diagnosis may predict a more benign disease course. IT is associated with haematological malignancy and carries better prognosis and response to treatment.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease The effect of increased water intake on kidney cyst growth in patients with polycystic kidney disease was compared for two groups randomly assigned to either prescribed or ad libitum water intake. Over 3 years, there was no difference in height-corrected total kidney volume between the groups.

Estimating the glomerular filtration rate in pregnancy: The evaluation of the Nanra and CKD-EPI serum creatinine-based equations.

AIM: To compare the performance of the Nanra and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate in pregnancy against the 24 h urine creatinine clearance. METHODS: Pregnant women had 24 h urine collections with simultaneous serum creatinine levels. Measured 24 h urine creatinine clearance was compared to two equations: Nanra and CKD-EPI. Level of concordance was measured, with an a priori bias acceptance of ±15 ml/min/1.73 m2. RESULTS: A total of 53 synchronous urine and serum creatinine samples were analysed. The Nanra equation had a bias of -13.4 ml/min/1.73 m2 while the CKD-EPI equation had bias of 14.2 ml/min/1.73 m2. Both equations showed a high degree of proportional error and had poor agreement with 24 h urine creatinine clearance. CONCLUSIONS: None of the equations were shown to reliably measure the estimated glomerular filtration rate in pregnant women. A valid serum creatinine-based estimated glomerular filtration rate equation in pregnancy is yet to be established.

Assessment of Dietary Sodium Intake Using the Scored Salt Questionnaire in Autosomal Dominant Polycystic Kidney Disease.

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ; a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 during the screening visit of the PREVENT-ADPKD trial. High dietary sodium intake (HSI) was defined by a mean 24-h urinary sodium excretion ≥ 100 mmol/day from two collections. The median 24-h urine sodium excretion was 132 mmol/day (IQR: 112-172 mmol/d) (n = 75; mean age: 44.6 ± 11.5 years old; 53% female), and HSI (86.7% of total) was associated with male gender and higher BMI and systolic blood pressure (p < 0.05). The SSQ score (73 ± 23; mean ± SD) was weakly correlated with log10 24-h urine sodium excretion (r = 0.29, p = 0.01). Receiving operating characteristic analysis showed that the optimal cut-off point in predicting HSI was an SSQ score of 74 (area under the curve 0.79; sensitivity 61.5%; specificity 90.0%; p < 0.01). The evaluation of the SSQ in participants with a BMI ≥ 25 (n = 46) improved the sensitivity (100%) and the specificity (100%). Consumers with an SSQ score ≥ 74 (n = 41) had higher relative percentage intake of processed meats/seafood and flavourings added to cooking (p < 0.05). In conclusion, the SSQ is a valid tool for identifying high dietary salt intake in ADPKD but its value proposition (over 24-h urinary sodium measurement) is that it may provide consumers and their healthcare providers with insight into the potential origin of sodium-rich food sources.

Calcitriol loading before total parathyroidectomy with autotransplant in patients with end-stage kidney disease: does it prevent postoperative hypocalcaemia?

BACKGROUND: Hungry bone syndrome (HBS) is one of the most serious complications following parathyroidectomy for severe hyperparathyroidism. There is a lack of literature informing the treatment and risk factors for this condition and the ideal pre-operative strategy for prevention. AIMS: The primary aims were to examine the incidence of HBS with pre-operative calcitriol loading for 10 days and to determine the risk factors for HBS. The secondary aims were to determine the rate of intravenous calcium replacement in those with HBS and to assess whether cinacalcet removal has increased rates of parathyroidectomy in the end-stage kidney disease population. METHODS: We performed a retrospective study from 2011 to 2018 on 45 patients with end-stage kidney disease undergoing total parathyroidectomy with autotransplantation for severe hyperparathyroidism. This was based at the John Hunter and Newcastle Private Hospitals in New South Wales. RESULTS: 28.3% of patients with calcitriol loading undergoing parathyroidectomy fulfilled criteria for HBS. Pre-operative variables that were associated with HBS were elevated parathyroid hormone (P = 0.028) and longer duration of renal replacement therapy (P = 0.033). Rates of total parathyroidectomy were higher after the removal of calcimimetics from the Pharmaceutical Benefits Scheme (P = 0.0024). CONCLUSIONS: HBS remains a common complication of parathyroidectomy, even with prolonged high-dose calcitriol loading. This emphasises the need for further trials investigating other targeted therapies, such as bisphosphonates, to prevent HBS. Those most at risk of HBS are patients with high bone turnover and prolonged renal replacement therapy.

Metastatic lung adenocarcinoma- associated thrombotic microangiopathy in a renal transplant recipient.

Thrombotic microangiopathy (TMA) after renal transplantation can be a diagnostic challenge. TMA can occur with calcineurin inhibitors, allograft rejection, infection, mutations in complement regulatory proteins and autoimmunity. A 52-year-old male renal transplant recipient presented with extensive deep vein thrombosis. He developed transfusion-dependent microangiopathic haemolytic anaemia with thrombocytopenia. He did not respond calcineurin inhibitor cessation, eculizumab or plasma exchange. ADAMTS13 and complement levels were normal. Infection and autoimmune screens were negative. A diagnosis of metastatic adenocarcinoma was made on bone marrow biopsy. This represents a rare case of malignancy-associated TMA in a renal transplant recipient. Early diagnosis can facilitate the prompt initiation of chemotherapy which is the only treatment option.

Randomised controlled trial to determine the efficacy and safety of prescribed water intake to prevent kidney failure due to autosomal dominant polycystic kidney disease (PREVENT-ADPKD).

INTRODUCTION: Maintaining fluid intake sufficient to reduce arginine vasopressin (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). However, evidence to support this as a clinical practice recommendation is of poor quality. The aim of the present study is to determine the long-term efficacy and safety of prescribed water intake to prevent the progression of height-adjusted total kidney volume (ht-TKV) in patients with chronic kidney disease (stages 1-3) due to ADPKD. METHODS AND ANALYSIS: A multicentre, prospective, parallel-group, open-label, randomised controlled trial will be conducted. Patients with ADPKD (n=180; age ≤65 years, estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2) will be randomised (1:1) to either the control (standard treatment+usual fluid intake) or intervention (standard treatment+prescribed fluid intake) group. Participants in the intervention arm will be prescribed an individualised daily fluid intake to reduce urine osmolality to ≤270 mOsmol/kg, and supported with structured clinic and telephonic dietetic review, self-monitoring of urine-specific gravity, short message service text reminders and internet-based tools. All participants will have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and 36 months. The primary end point is the annual rate of change in ht-TKV as determined by serial renal MRI in control vs intervention groups, from baseline to 3 years. The secondary end points are differences between the two groups in systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient adherence, acceptability and safety. ETHICS AND DISSEMINATION: The trial was approved by the Human Research Ethics Committee, Western Sydney Local Health District. The results will inform clinicians, patients and policy-makers regarding the long-term safety, efficacy and feasibility of prescribed fluid intake as an approach to reduce kidney cyst growth in patients with ADPKD. TRIAL REGISTRATION NUMBER: ANZCTR12614001216606.

Acute alveolar haemorrhage in hepatitis C-related cryoglobulinaemic vasculitis.

We describe a patient with untreated hepatitis C virus (HCV) infection presenting with pulmonary renal syndrome. He rapidly developed bilateral lung infiltrates and respiratory failure, and bronchoscopy confirmed acute alveolar haemorrhage secondary to cryoglobulinaemic vasculitis. Early bronchoscopy to confirm the diagnosis and consequent institution of immunosuppressive therapy led to excellent outcomes, which otherwise is reported in the literature to carry significant mortality. Therefore, in patients with HCV presenting with bilateral lung infiltrates, physicians must maintain a high degree of clinical suspicion for alveolar haemorrhage secondary to cryoglobulinaemic vasculitis.

Successful renal transplantation in a patient with cold agglutinin disease.

Cold agglutinin disease is a rare cause of acute graft loss after renal transplantation. A 71-year-old female with end stage renal failure was diagnosed to have cold agglutinin disease when investigated for recurrent clotting of hemodialysis circuits. Kidney transplantation was a major challenge due to unavoidable exposure of the transplant kidney to cold temperatures. Large volume plasma exchange given pre-transplant and infusion of warm saline prior to anastomosis resulted in successful renal transplantation with good graft function despite initial delayed graft function. This challenging case illustrates the complete removal of cold agglutinin antibodies with therapeutic large volume plasma exchange. J. Clin. Apheresis 32:56-58, 2017. © 2016 Wiley Periodicals, Inc.

Atrial fibrillation and warfarin use in haemodialysis patients: an individualized holistic approach is important in stroke prevention.

Incidence and prevalence of atrial fibrillation (AF) is higher in haemodialysis (HD) population than general population. AF is associated with higher morbidity and mortality than sinus rhythm in this population. The purpose of this review is to summarize all available evidence regarding use of warfarin in HD patients with AF for stroke prevention. The enormous heterogeneity of available studies does not allow pooling of the data in the form of meta-analysis or systematic review. Current evidence regarding use of warfarin for AF in terms of risk benefit ratio in this population is limited and conflicting. Randomized control trials evaluating the safety and efficacy of anticoagulation in this population by means of risk/benefit assessment tools are urgently needed. However, suitable HD patients with AF should be counselled on their likelihood of reduction of stroke risk and experiencing side-effects before initiating anticoagulant therapy. It is particularly important to incorporate the patient's preferences and willingness to trade off benefit and risk in stroke prevention. An individualized holistic approach optimizing all potential risk factors of bleeding and ischemic stroke in HD patients with AF is recommended.

The association between reduced GFR and hearing loss: a cross-sectional population-based study.

BACKGROUND: Chronic kidney disease (CKD) has long been associated with hearing loss in certain syndromes. Reported evidence to date has come from only small observational studies. We present the first community-based study to show an association between nonsyndromal CKD and hearing loss. STUDY DESIGN: Cross-sectional population-based study to examine the relationship between CKD and age-related hearing loss. SETTING & PARTICIPANTS: The Blue Mountains Hearing Study is a survey of age-related hearing loss conducted in 1997-2004; a total of 2,564 participants had audiometric testing and complete renal data. PREDICTOR OR FACTOR: Moderate CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). OUTCOMES: Bilateral hearing loss, defined as average pure-tone threshold >25 dB for measurements at frequencies of 0.5, 1.0, 2.0, and 4.0 kHz. MEASUREMENTS: Baseline biochemistry tests, including serum creatinine, were performed. Pure-tone audiometry was performed in sound-treated booths. RESULTS: Moderate CKD was present in 513 of 2,564 participants. Of persons with moderate CKD, 279 (54.4%) had measured hearing loss compared with 581 (28.3%) with eGFR ≥60 mL/min/1.73 m(2). Moderate CKD was independently associated with hearing loss (OR, 1.43; 95% CI, 1.10-1.84; P = 0.006) after adjusting for age; sex; noise exposure; education; diabetes, hypertension, and stroke histories; and smoking. Participants with eGFR <45 mL/min/1.73 m(2) had the highest prevalence of hearing loss (73%) compared with those with eGFR ≥90 mL/min/1.73 m(2) (19%; multivariate adjusted OR, 2.4 [95% CI, 1.3-4.5]). Analyses were repeated after excluding participants reporting furosemide use (a known ototoxic agent); the association between moderate CKD and hearing loss remained significant (multivariate adjusted OR, 1.40 [95% CI, 1.08-1.83]; P = 0.01). LIMITATIONS: The present study is not longitudinal and does not permit causal inference from the observed associations. CONCLUSIONS: Moderate CKD per se was associated independently with hearing loss. Recognizing this link could lead to earlier hearing assessment with appropriate interventions to preserve the hearing of patients with CKD.

Emerging therapies for chronic kidney disease: what is their role?

The prevalence of chronic kidney disease (CKD) is increasing worldwide. The best therapies currently available focus on the control of blood pressure and optimization of renin-angiotensin-aldosterone system blockade. Currently available agents are only partially effective against hard end points such as the development of end-stage renal disease and are not discussed in this Review. Many other agents have been shown to reduce proteinuria and delay progression in animal models of CKD. Some of these agents, including tranilast, sulodexide, thiazolidinediones, pentoxifylline, and inhibitors of advanced glycation end-products and protein kinase C, have been tested to a limited extent in humans. A small number of randomized controlled human trials of these agents have used surrogate markers such as proteinuria as end points rather than hard end points such as end-stage renal disease or doubling of serum creatinine level. Emerging therapies that specifically target and reverse pathological hallmarks of CKD such as inflammation, fibrosis and atrophy are needed to reduce the burden of this chronic disease and its associated morbidity. This Review examines the evidence for emerging pharmacological strategies for slowing the progression of CKD.

Monoclonal gammopathy and glomerulopathy associated with chronic lymphocytic leukemia.

BACKGROUND: A 42-year-old previously healthy man was referred to hospital with an 8-week history of fevers, night sweats, fatigue, and unintentional weight loss. There was no past history of medical illness or any medication use. Physical examination was unremarkable. On urinalysis, the patient had hematuria (grade 4+) and proteinuria (grade 4+). INVESTIGATIONS: Urine phase-contrast microscopy, full blood count, renal function tests, 24-h urine collection for protein, serum immune electrophoresis, renal biopsies, phase-contrast microscopy, serological tests for antinuclear antibodies, extractable nuclear antigens, antineutrophil cytoplasmic antibodies, hepatitis B, hepatitis C and HIV, cryoglobulin test, complement testing, flow cytometry of the peripheral blood, and bone marrow biopsy. DIAGNOSIS: Monoclonal gammopathy and a glomerulopathy, with microtubular deposits, associated with chronic lymphocytic leukemia. MANAGEMENT: Treatment with prednisone and cyclophosphamide did not improve proteinuria, although lymphocyte count returned to normal. The patient did not tolerate high-dose cyclophosphamide and was started on rituximab. His proteinuria completely resolved and there was complete disappearance of the microtubules.