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Objectives Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. Methods We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with life-threatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction. Results A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4–200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11–58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19–58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20–112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. Conclusions The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.

Background Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate. Methods Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy ( n  = 20) or TAC combined with MMF ( n  = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function. Results 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group ( p  = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group ( p  = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group ( p  = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment. Conclusions Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN. Trial registration This trial is registered with EudraCTN2008–001009-41 . Trial registration date 2008-10-08.

There is good evidence supporting more extensive use of metformin in type 2 diabetes, in reducing morbidity and mortality. The evidence for a real problem from metformin-induced lactic acidosis is weak, and the risks of alternative agents are often overlooked. We have examined the available data regarding metformin that might cause concern in patients with kidney disease, and find it to be extremely limited. There is no good data on which to offer guidance, but it seems likely that metformin can be used in patients with GFR 60–90 ml/min but at reduced dose at lower levels of GFR, and can probably be safely used at GFRs from 30–60 ml/min but with the same caution as with any renally excreted drug. The risks (often overlooked) and benefits of alternative hypoglycaemic agents should be considered carefully. The overall evidence that metformin causes major harm is poor.

Blood sampling, despite its historical significance in clinical diagnostics, poses challenges, such as invasiveness, infection risks, and limited temporal fidelity for continuous monitoring. In contrast, exhaled breath offers a noninvasive, pain-free, and continuous sampling method, carrying biochemical information through volatile compounds like ammonia (NH3). NH3 in exhaled breath, influenced by kidney function, emerges as a promising biomarker for renal health assessment, particularly in resource-limited settings lacking extensive healthcare infrastructure. Current analytical methods for breath NH3, though effective, often face practical limitations. In this work, we introduce a low-cost, internet-connected, paper-based wearable device for measuring exhaled NH3, designed for early detection of kidney dysfunction at the point of need. The device, which attaches to disposable face masks, utilizes an array of disposable paper-based sensors to detect NH3 with the readout being changes in electrical impedance that correlate with the concentration of NH3. The sensor array is housed in a biodegradable plastic enclosure to mitigate high relative humidity issues in breath analysis. We validated our technology using a laboratory setup and human subjects who consumed ammonium chloride-containing candy to simulate elevated breath NH3. Our wearable sensor offers a promising solution for rapid, point-of-need kidney dysfunction screening, particularly valuable in resource-limited settings. This approach has potential applications beyond kidney health monitoring, including chemical industry safety and environmental sensing, paving the way for accessible, continuous health monitoring.

Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Patients have been described who have both anti-neutrophil cytoplasm antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies. We have attempted to define the true prevalence of such “double positive” patients, and describe in detail their clinical features and outcome. We have reviewed all serologic assays performed between 1990 and 2000 in a single institution, and the case notes of patients having sera positive for both ANCA and anti-GBM antibodies. During this time 20,392 sera were initially tested for ANCA, and 4808 sera tested for anti-GBM antibodies. Five percent of all ANCA-positive serum samples were also positive for anti-GBM antibodies, and 32% of all anti-GBM positive samples had detectable ANCA. Of 27 patients with both antibodies, 82% had anti-myeloperoxidase specific P-ANCA. Pulmonary hemorrhage occurred in 44%. Renal biopsy showed extensive glomerular cellular crescents in most patients. Patient and renal survival rates were 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis-dependent at presentation, and none of these recovered renal function, despite immunosuppression with or without plasma exchange. Serologic evidence of double positivity for both ANCA and anti-GBM antibodies is common in patients with either antibody. In our study these patients have a poor prognosis when presenting with severe disease and initially behave more like anti-GBM disease than vasculitis. Recovery from severe renal failure is rare.

Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear. We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies. The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23-74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22-2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65-1898); P = 0.18 Mann-Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis. We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

The idea that antibodies to GBM might be pathogenic dates back to 1967 when [Lerner RA], Glassock, and Dixon, in a classic series of experiments, transferred antibodies eluted from kidneys of patients with [Ernest William Goodpasture]'s disease to squirrel monkeys, which subsequently developed glomerulonephritis.9 Rapid disease recurrence occurs if transplantation is done in the presence of circulating antibody to GBM and correlations have been reported between disease severity and antibody titre.8 As a result, much of the work aimed at understanding the disease has revolved around the humoral immune response--antibodies to GBM and their epitopes. This culminated in the discovery of the autoantigen within the GBM to which these antibodies bind, which was found to be the non-collagenous domain of the (alpha)3 chain of type IV collagen--(alpha)3(IV)NCl.10 Precise epitopes within this molecule to which most patients' antibodies bind have been located at the amino terminus. More recently, the role of cell mediated immunity in triggering Goodpasture's disease has become apparent, with evidence of autoreactive T lymphocytes directed against the same (alpha)3(IV)NCI antigen.11 The factors initiating the activity of these cells in patients but not in healthy people remain unknown. Since HLA DR15 and DR4 alleles are common within the Caucasian population (being found in about 30%) other genetic or environmental factors must be involved in initiating the disease.

BackgroundRenal disease is an emerging problem in patients living with human immunodeficiency virus (HIV), as illustrated by an increased incidence of acute kidney injury and chronic kidney disease (CKD) from HIV, its associated treatment and comorbidities such as diabetes and vascular disease. We have established a combined HIV-renal clinic to manage such patients, enhance their treatment and minimize outpatient visits.MethodsWe have analysed the outcomes of the first 99 patients seen in the clinic using electronic patient records. These ninety-nine patients were referred to the service from HIV physicians in West London and all the patients were seen jointly by an HIV and a renal consultant.ResultsSixty-five percent of the patients were referred with reduced renal function or proteinuria [mean creatinine at presentation 136 mcmol/L, estimated glomerular filtration rate (eGFR) 57 mL/min/1.73 m2]. The majority (53%) had risk factors predisposing to vascular disease including diabetes, hypertension, previous stroke or myocardial infarction. Overall, 27% of patients had a renal diagnosis directly associated with HIV (HIVAN, immune complex nephritis, tenofovir toxicity, Fanconi syndrome), 73% had an alternative possible cause. Twenty-seven percent of patients had low-level proteinuria (urine protein:creatinine ratio abnormal but <100 mg/mmol) or mildly reduced eGFR (40–66 mL/min/1.73 m2) without a clear underlying cause. Ten percent of patients were thought to have tenofovir-induced renal damage all of whom improved on cessation of this agent. Following the review in the combined clinic, 64% of patients had a change in treatment or management, with 50% improving their renal parameters as a result. Most patients were discharged back to their main HIV teams for ongoing follow-up.ConclusionsA combined HIV-renal clinic can enhance patient care with reduced outpatient visits.

HIV infection is an independent risk factor for end-stage kidney disease in HIV-positive patients of black ethnicity. Highly effective antiretroviral therapy has allowed these patients to be considered for kidney transplantation (KT). We report the outcomes of KT in a national observational cohort study. We retrospectively identified HIV-positive patients who had undergone KT up to December, 2010, through all 25 UK KT centres and major HIV clinics, and included follow-up until December, 2011. Patient characteristics, treatments, and complications were described. Patient and graft survival rates and cumulative incidence of acute rejection were estimated with Kaplan-Meier and Nelson-Aalen analyses. 35 HIV-positive KT recipients (median age 40 years, 66% male, 74% black ethnicity) were identified. At the time of KT, all patients were stable on antiretroviral therapy with undetectable HIV RNA and median CD4 cell count of 366 cells per mL. Patient survival at both 1 and 3 years was 91·3%, and graft survival was 91·3% and 84·7%, respectively. In the first year after KT, blood concentrations of calcineurin inhibitors (CNI) were frequently outside the therapeutic reference range. At 1 year after KT, the cumulative incidence of acute allograft rejection was 48%, and the median estimated glomerular filtration rate 61 mL/min/1·73 m2 (IQR 46–78). Although HIV viraemia and HIV disease progression were uncommon, renal complications were relatively frequent. Our study corroborates the feasibility of KT in HIV-positive patients. Co-administration of antiretroviral therapy and CNI is challenging, and sub-therapeutic CNI concentrations may contribute to the high rate of acute allograft rejection. The optimum immune suppression strategy in this population remains to be refined. King's College London.

Blood sampling, despite its historical significance in clinical diagnostics, poses challenges such as invasiveness, infection risks, and limited temporal fidelity for continuous monitoring. In contrast, exhaled breath offers a non-invasive, pain-free, and continuous sampling method, carrying biochemical information through volatile compounds like ammonia (NH3). NH3 in exhaled breath, influenced by kidney function, emerges as a promising biomarker for renal health assessment, particularly in resource-limited settings lacking extensive healthcare infrastructure. Current analytical methods for breath ammonia, though effective, often face practical limitations. In this work, we introduce a low-cost, internet-connected, paper-based wearable device for measuring exhaled ammonia, designed for early detection of kidney dysfunction at the point-of-need. The device, which attaches to disposable facemasks, utilizes a disposable paper-based sensor array housed in a biodegradable plastic enclosure to mitigate high relative humidity (RH) issues in breath analysis. We validated our technology using a laboratory setup and human subjects who consumed ammonium chloride-containing candy to simulate elevated breath ammonia. Our wearable sensor offers a promising solution for rapid, point-of-need kidney dysfunction screening, particularly valuable in resource-limited settings. This approach has potential applications beyond kidney health monitoring, including chemical industry safety and environmental sensing, paving the way for accessible, continuous health monitoring.