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Vol. 41. Issue. 1.January - February 2021
Pages 1-90
Vol. 41. Issue. 1.January - February 2021
Pages 1-90
Letter to the Editor
Open Access
IgA nephropathy: Short term effects of prednisone treatment on proteinuria, renal function and relation with Oxford classification
Nefropatía IgA: efectos a corto plazo del tratamiento con prednisona sobre la proteinuria, función renal y relación con la clasificación de Oxford
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Enoc Merino García
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enocmerino@gmail.com

Corresponding author.
, Francisco José Borrego Utiel, María José García Cortés
Unidad de Gestión Clínica de Nefrología, Hospital Universitario de Jaén, Jaén, Spain
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Table 1. Progression of renal function, proteinuria and albuminuria after treatment with prednisone in patients with IgA nephropathy.
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Dear Editor,

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The clinical variables most commonly associated with the risk of developing end-stage renal disease (ESRD) for IgA nephropathy are the degree of proteinuria, reduced baseline glomerular filtration rate and arterial hypertension.1 Given the great variety of histological lesions of IgAN, their description was homogenised and variables that had prognostic significance for renal impairment were sought, developing the Oxford classification,2,3 which has been validated in various studies.3,4 In IgAN the demonstration of efficacy of any therapeutic strategy is very difficult given the slow progression of the disease and the need for very long follow-up studies. The use of steroids is recommended in cases with proteinuria >1g/day and glomerular filtration rate >50ml/min/1.73m2, although positive responses have also been observed with lower glomerular filtration rates,5 achieving better preservation of renal function, reduction of proteinuria and microhaematuria,5–7 although with common adverse effects.6,8 The response to steroids appears to be greater in patients with mesangial and endocapillary proliferation, glomerulosclerosis and even tubulointerstitial fibrosis,5 although the prognosis is not clear in relation to the Oxford classification.

Our objective in this study was to review the short-term response of renal function and proteinuria in patients with IgAN who were treated with corticosteroids, taking into account the histological parameters of the Oxford classification. We reviewed patients who had received corticosteroid treatment for a minimum of 6 months. The study included 33 patients aged 41±13 years, 23 (69.7%) were men, with a mean weight of 73.2±12.4kg. In total, 19 patients were taking ACE inhibitors, seven were receiving angiotensin II receptor blockers (ARBs) and seven dual blockade. All had been on this treatment for at least six months before starting steroid treatment (mean treatment time of 14 months). We administered prednisone at a starting dose of 40−80mg/day (<1mg/kg/day) for 2–3 weeks, with a subsequent gradual decrease of 10mg/every 2–3 weeks until reaching 10mg/day as a maintenance dose for six months. If proteinuria had decreased <250mg/day before six months had elapsed, it was reduced until it was discontinued at three months. The starting dose of prednisone was 57±6mg/day (median 60) and 0.8±0.1mg/kg/day. In six patients, cyclophosphamide was given associated to prednisone (50mg/day in one patient, 100mg/day in four and 125mg/day in one) for up to six months. The prevalence of the Oxford variables was: M1 63.6%; E1 42.4%; S1 45.5%; T0 39.4%, T1 45.5% and T2 3%; C 27.3%.

In terms of progression, we observed a significant decrease in proteinuria and albuminuria at six and twelve months, without observing significant changes in renal function (Table 1). Proteinuria decreased in 72.7% of the patients at six months and in 81.8% at twelve months. The median reduction in proteinuria was 40% at six months and 45.8% at twelve months.

Table 1.

Progression of renal function, proteinuria and albuminuria after treatment with prednisone in patients with IgA nephropathy.

  Baseline  6 months  12 months  p-Valuea 
Creatinine (mg/dl)  1.6±0.8  1.6±0.7  1.8±1.1  NS 
eGFR-MDRD (ml/min/1.73m258±28  58±25  52±24  NS 
Proteinuria (mg/gCr)  1675±1998  1185±1498  1023±1496  <0.001 
Albuminuria (mg/gCr)  1023±1134  806±1028  667±973  0.003 
[0,1–5] Progression of proteinuria (mg/gCr) according to the Oxford classification (MEST-C)
Mesangial hyp. 0  1050±1089  396±288  392±298  0.09 
Mesangial hyp. 1  2023±2339  1552±1732  1313±1787  0.002 
Endocapillary prol. 0  1562±1510  959±937  699±546  0.014 
Endocapillary prol. 1  1960±2633  1527±2032  1444±2169  0.024 
Segm. sclerosis 0  2157±2658  1625±1981  1554±2096  NS 
Segm. sclerosis 1  1378±1388  867±968  597±634  0.001 
Tub. atrophy/Int. fib. 0  1311±989  825±1052  1079±1836  NS 
Tub. atrophy/Int. fib. 1  1595±1733  1212±1231  743±725  0.002 
Extracapillary prol. 0  1674±1550  1183±1168  1053±1481  0.005 
Extracapillary prol. 1  2027±3060  1462±2277  1157±1801  0.016 

A significant decrease in proteinuria and albuminuria is broadly observed at six and twelve months after treatment, without significant changes in renal function. Upon stratification according to the histological parameters of the Oxford classification, we observed a decrease in proteinuria in each stratum of the Oxford classification parameters.

NS: not significant.

a

Friedman test.

Table 1 shows the progression of proteinuria according to the MEST-C parameters of the Oxford classification. Baseline proteinuria was higher in patients showing: mesangial hyperplasia, endocapillary proliferation, interstitial fibrosis/tubular atrophy and extracapillary proliferation, although it did not reach statistical significance. In terms of progression, we observed a general reduction in proteinuria levels in practically all the strata considered on the MEST-C score. The presence of arteriolar hyalinosis, muscle hyperplasia or arterial intimal proliferation did not appear to have any influence.

In some studies, a worse response to treatment has been observed in cases with M1 mesangial proliferation, S1 segmental sclerosis and T1/T2 tubular atrophy.9 However, other publications have shown that the use of corticosteroids reduce proteinuria and the rate of kidney impairment progression by a similar amount in both strata of the Oxford classification variables.5 In our case, despite higher proteinuria and worse baseline renal function in categories 1 versus 0 of the MEST-C variables, we observed a reduction in proteinuria in all the strata studied. When renal biopsies were repeated after treatment, an improvement was observed in all proliferative parameters and in changes in fibrosis and tubular atrophy when corticosteroids are used,10 which could explain the lack of correlation with the baseline histological parameters of the Oxford classification.

Therefore, in patients with IgAN, steroid treatment may reduce proteinuria regardless of MEST-C characteristics. There is a lack of studies that clarify the degree of response to be expected after the use of steroids on glomerular filtration rate decline that take into account each prognostic variable of the MEST-C classification.

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Please cite this article as: Merino García E, Borrego Utiel FJ, García Cortés MJ. Nefropatía IgA: efectos a corto plazo del tratamiento con prednisona sobre la proteinuria, función renal y relación con la clasificación de Oxford. Nefrologia. 2021;41:71–74.

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