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      Adult minimal-change disease: observational data from a UK centre on patient characteristics, therapies, and outcomes

      research-article
      , ,
      BMC Nephrology
      BioMed Central
      Minimal change disease, Outcomes, Patient characteristics, Treatments

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          Abstract

          Background

          Minimal change disease (MCD) is a common cause of the nephrotic syndrome in adults with limited evidence on its treatment and prognosis. We examined the presenting characteristics, treatments, and outcomes of adult patients with MCD in our centre.

          Methods

          This was an observational cohort study using retrospectively-collected data. All patients who had a renal biopsy reported as MCD between 1996 and 2012 were included, and data were collected at baseline and during follow-up. Statistical analysis included Cox-regression analysis to examine which factors were associated with risk of relapse.

          Results

          Seventy-eight patients were included, and had a median age of 36 years, and were 60% male and 73% white. Median follow-up time was 72 months. 37% were in AKI at presentation, which was significantly associated with a lower serum albumin and older age. Although 10% were steroid-resistant, 98% achieved remission at a median time of 5 weeks. 61% relapsed, at a median time of 11 months, and patients had a median number of 2 relapses during follow-up. A higher eGFR was associated with an increased risk of relapse (hazard ratio 1.18 [1.03–1.36] per 10 mL/min increase in eGFR), and females were significantly more likely than males to have an early relapse. Nearly half of the cohort required an additional immunosuppressive agent on top of glucocorticoids, the most commonly used being calcineurin inhibitors. Five patients subsequently developed FSGS: these patients had a lower baseline creatinine, a higher serum albumin, a longer time to remission, and were more likely to be steroid-resistant. Follow-up renal function was generally preserved, but follow-up creatinine was higher in those who had presented with AKI, and in those who had been commenced on a RAS inhibitor after biopsy. Infection requiring admission, diabetes mellitus and venous thromboembolism developed in 14%, 12%, and 12% of patients respectively.

          Conclusions

          Nearly all adults with MCD achieve remission, but relapses and disease- and therapy-related complications are common. In our cohort, eGFR and gender were associated with risk of relapse, and these previously undescribed associations could be explored further in future work.

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          Most cited references22

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          Adult minimal-change disease: clinical characteristics, treatment, and outcomes.

          Minimal-change disease (MCD) counts for 10 to 15% of cases of primary nephrotic syndrome in adults. Few series have examined this disease in adults. A retrospective review was performed of 95 adults who had MCD and were seen at a single referral center. Examined were presenting features, response to daily versus alternate-day steroids, response to second-line agents, relapse patterns, complications of the disease and therapy, presence of acute renal failure (ARF), and outcome data. Sixty-five patients received daily and 23 received alternate-day steroids initially. There were no differences in remissions, time to remission, relapse rate, or time to relapse between daily- and alternate-day-treated patients. More than one quarter of patients were steroid resistant. At least one relapse occurred in 73% of patients; 28% were frequently relapsing. A significant proportion of frequently relapsing patients became steroid dependent. Second-line agents were used for steroid dependence, steroid resistance, or frequent relapses. No single agent proved superior. There were more remissions with second-line agents in steroid-dependent patients compared with steroid-resistant patients, and remissions were more likely to be complete in steroid-dependent patients. ARF occurred in 24 patients; they tended to be older and hypertensive with lower serum albumin and more proteinuria than those without ARF. At follow up, patients with an episode of ARF had higher serum creatinine than those without ARF. Four patients progressed to ESRD. These patients were less likely to have responded to steroids and more likely to have FSGS on repeat renal biopsy. In this referral MCD population, response to daily and alternate-day steroids is similar. Second-line agents give greater response in patients who are steroid dependent. ARF occurs in a significant number of adult MCD patients and may leave residual renal dysfunction. Few patients progress to ESRD.
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            Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997.

            Data compiled during the 1970s and early 1980s indicated that during these periods, membranous nephropathy was the most common cause of unexplained nephrotic syndrome in adults, followed in order of frequency by minimal-change nephropathy and focal segmental glomerulosclerosis (FSGS). However, we and others recently reported an increase in the incidence of FSGS over the past two decades, and the number of cases of FSGS diagnosed by renal biopsies in these centers now exceeds the number of cases of membranous nephropathy. Nonetheless, as a substantial fraction of patients with FSGS do not have the nephrotic syndrome, it remained unclear as to what extent the relative frequencies of FSGS and other glomerulopathies as causes of the nephrotic syndrome have changed over this time. To address this concern, we reviewed data from 1,000 adult native kidney biopsies performed between January 1976 and April 1979 and from 1,000 biopsies performed between January 1995 and January 1997, identified all cases with a full-blown nephrotic syndrome of unknown etiology at the time of biopsy, and compared the relative frequencies with which specific diseases were diagnosed in these latter cases between the two time intervals. The main findings of this study were that, first, during the 1976 to 1979 period, the relative frequencies of membranous (36%) and minimal-change (23%) nephropathies and of FSGS (15%) as causes of unexplained nephrotic syndrome were similar to those observed in previous studies during the 1970s and early 1980s. In contrast, from 1995 to 1997, FSGS was the most common cause of this syndrome, accounting for 35% of cases compared with 33% for membranous nephropathy. Second, during the 1995 to 1997 period, FSGS accounted for more than 50% of cases of unexplained nephrotic syndrome in black adults and for 67% of such cases in black adults younger than 45 years. Third, although the relative frequency of nephrotic syndrome due to FSGS was two to three times higher in black than in white patients during both study periods, the frequency of FSGS increased similarly among both racial groups from the earlier to the later period. Fourth, the frequency of minimal-change nephrotic syndrome decreased from the earlier to the later study period in both black and white adults. Fifth, the relative frequency of membranoproliferative glomerulonephritis as a cause of the nephrotic syndrome declined from the 1976 to 1979 period to the 1995 to 1997 period, whereas that of immunoglobulin A nephropathy appeared to increase; the latter accounted for 14% of cases of unexplained nephrotic syndrome in white adults during the latter study period. Finally, 10% of nephrotic adults older than 44 years had AL amyloid nephropathy; none of these patients had multiple myeloma or a known paraprotein at the time of renal biopsy.
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              Clinicopathologic correlations of renal pathology in Spain.

              There are not enough large epidemiologic population-based studies of biopsy-proven nephropathies with detailed clinicopathologic correlations. The Glomerulonephritis Registry of the Spanish Society of Nephrology has obtained data from 9378 cases with native biopsy-proven renal diseases and well-known clinical syndrome between 1994 and 2001, investigating clinicopathologic correlations. Patients were divided in three groups according to age: children ( 65 years). The most common clinical syndrome at any age is nephrotic syndrome (35.5%), followed by asymptomatic urinary abnormalities (25.9%), acute renal failure (12.9%), chronic renal failure (12.1%), nephritic syndrome (4.5%), macroscopic haematuria (4.5%), and arterial hypertension (3.0%). A male predominance is observed at any age (3:2). The frequencies of histologic findings are statistically different in all syndromes according to age. Minimal change disease is the most frequent finding in children with nephrotic syndrome (39.5%), whereas in adults and elderly, membranous nephropathy is the most prevalent (24.2% and 28.0%, respectively). Ig A nephropathy (IgAN) is the most frequent glomerulonephritis in patients with asymptomatic urinary abnormalities at any age. Acute renal failure is an important cause for performing a kidney biopsy in elderly and vasculitis is the main histologic finding. The clinical manifestations of focal segmental glomerulosclerosis, non-IgA mesangial nephropathy, lupus nephritis, vasculitis, and nephroangiosclerosis are statistically different according to age. The findings of clinicopathologic correlations obtained from the Spanish Registry of Glomerulonephritis on native biopsy-proven renal diseases add valuable information to previous reports and it can be the initial step for follow-up and prospective studies.
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                Author and article information

                Contributors
                anthony.fenton@uhb.nhs.uk
                stuart.smith@uhb.nhs.uk
                peter.hewins@uhb.nhs.uk
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                16 August 2018
                16 August 2018
                2018
                : 19
                : 207
                Affiliations
                ISNI 0000 0004 0376 6589, GRID grid.412563.7, Department of Renal Medicine, Elizabeth Hospital Birmingham, , University Hospitals Birmingham NHS Foundation Trust, ; Birmingham, UK
                Author information
                http://orcid.org/0000-0003-2665-6924
                Article
                999
                10.1186/s12882-018-0999-x
                6097194
                30115013
                06a8d263-e7a4-4c07-8a6b-564a87aa13e8
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 June 2017
                : 3 August 2018
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Nephrology
                minimal change disease,outcomes,patient characteristics,treatments
                Nephrology
                minimal change disease, outcomes, patient characteristics, treatments

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