Focal segmental glomerulosclerosis (FSGS) is a well-defined pattern of glomerular injury identifiable on renal biopsy using light microscopy. FSGS is not a single entity and much information is ...needed to make a proper evaluation in each subject with the condition to identify the cause, prognosticate, and inform treatment choices. Categories of information required include: clinical presentation, responsiveness to steroids, pathological subtype, genetic background, and evidence for other adaptive, viral, and toxic causes. Primary FSGS describes a cohort of conditions identified by exclusion of known contributory causes, but does not represent a single entity. Clinical manifestations and outcomes of FSGS vary widely; they include asymptomatic proteinuria, cases of spontaneous remission, steroid-sensitive nephrotic syndrome, and nephrotic syndrome resistant to immune modulating therapy progressing to end-stage renal disease with recurrence after transplantation. Although immune modulating therapy (based notably on corticosteroids and calcineurin inhibitors) are widely used in primary FSGS, robust evidence of their efficacy remains scant.
On September 27–29, 2018, the International Symposium on IgA Nephropathy, organized by the International IgA Nephropathy Network, was held in Buenos Aires, Argentina, celebrating the 50th anniversary ...of the first description of IgA nephropathy by Berger and Hinglais in 1968. The meeting was attended by over 200 scientists and clinicians from 26 different countries across the globe. We report some key insights drawn from the meeting–including the molecular pathogenesis, genetics, pathology, and therapeutics of IgA nephropathy.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian ...subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world.
We will prospectively recruit 200 patients with IgAN (the GRACE IgANI-
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ndians-cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population.
Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 Other dated 23.07.2014 and IRB Min. No. 9481 Other dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.
Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.
To evaluate the efficacy and safety of corticosteroids in patients ...with IgA nephropathy at risk of progression.
The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate eGFR of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade and to provide follow-up until 335 primary outcomes occurred.
Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.
The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.
After randomization of 262 participants (mean age, 38.6 SD, 11.1 years; 96 37% women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% 95% CI, 4.8%-18.2%), mostly due to excess serious infections (11 8.1% vs 0; risk difference, 8.1% 95% CI, 3.5%-13.9%; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 95% CI, 0.17-0.85; risk difference, 10.0% 95% CI, 2.5%-17.9%; P = .02).
Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.
clinicaltrials.gov Identifier: NCT01560052.
An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway.
Newly referred South Asian and ...White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres--Luton, West London and Leicester--and their experiences of the diabetes and renal care recorded.A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups.
23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients.
The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers.
AbstractObjectiveTo determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative ...kidney management.DesignInternational cross sectional survey.SettingInternational Society of Nephrology (ISN) survey of 182 countries from July to September 2018.ParticipantsKey stakeholders identified by ISN’s national and regional leaders.Main outcome measuresMarkers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management.ResultsResponses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world’s population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management—namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with income level.ConclusionsThese comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease. They demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy.
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