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NDT Advance Access originally published online on September 15, 2006
Nephrology Dialysis Transplantation 2006 21(12):3357-3361; doi:10.1093/ndt/gfl508
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

IgA nephritis: ACE inhibitors, steroids, both or neither?

Francesco Locatelli, Claudio Pozzi and Simeone Andrulli

Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy

Correspondence and offprint requests to: Professor Francesco Locatelli, Department of Nephrology and Dialysis, Ospedale A Manzani, via dell'Eremo 9, 23900 Lecco, Italy. Email: nefrologia{at}ospedale.lecco.it

Keywords: ACE inhibitors; angiotensin II receptor blockers; Cytotoxic drugs; IgA Nephritis; renal progression; steroids; treatment



   Introduction
Top
 Introduction
What is the role...
 Are corticosteroids necessary...
 Are steroids alone always...
 What should be done...
 References
 
Immunoglobulin A nephropathy (IgAN), a disease characterized by the predominant deposition of IgA in the glomerular mesangium, is the most common glomerulonephritis in the world. No more than 10% of all patients experience complete remission of the urinary abnormalities, and IgAN frequently progresses towards chronic renal impairment, leading to end-stage renal disease in about 25% of the patients within 20 years [1]. Should this nephropathy be treated? If so, what is the best therapy? And should all patients be treated with the same drugs? The real problem is that, although some progress has been made in our pathogenetic understanding, the disease is still largely unknown and no specific treatment is available.

Given the variability of the clinical and histological manifestations of IgAN, it is perhaps not surprising that there is still no general consensus about the treatment of IgAN [2], other than fully controlling hypertension possibly with angiotensin-converting enzyme (ACE) inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs). Omega-3 fatty acids cannot reduce proteinuria and their ability to slow the progression of IgAN is uncertain. Tonsillectomy has not been tested in methodologically appropriate studies, and so its usefulness is also uncertain: we agree with Dr Appel [3] that ‘there are more data on the potential benefits of tonsillectomy in IgAN on the Internet than in the medical literature!’. Finally, a number of other proposed treatments (anticoagulants, antioxidants, statins) have led to inconclusive results. As this long list of alternative treatments indicates that none is convincing, this editorial will be limited to discussing the efficacy of ACEIs, ARBs and corticosteroids.



   What is the role of ACEIs and/or ARBs?
Top
 Introduction
 What is the role...
Are corticosteroids necessary...
 Are steroids alone always...
 What should be done...
 References
 
All patients with IgA nephropathy (or virtually any other renal disease) should be encouraged to achieve a blood pressure target of 125–130/75–80 mmHg, possibly by using ACEIs or ARBs, particularly if they are proteinuric. Unfortunately, this goal has not been reached even in many clinical studies, which underlines the difficulties of implementing guidelines in everyday clinical practice.

Seven randomized controlled trials of ACEIs and ARBs have been published in recent years [4–10], all of which have shown at least a short-term reduction in proteinuria and (when evaluated) slower progression to chronic kidney disease (CKD); these effects were more marked when an ACEI and ARB were administered together [7].

The rationale underlying the use of these drugs is strong and related to the role of angiotensin II in regulating renal haemodynamics and glomerular permselectivity. Angiotensin II causes glomerular hypertension and hyperfiltration, acts as a growth factor and a profibrogenetic cytokine, enhances the activation of nuclear factor-{kappa}B (NF-{kappa}B) and potentiates the renal sclerosis-promoting actions of platelet-derived growth factor (PDGF) and transforming growth factor (TGFß) [11]. Moreover, its overexpression in renal biopsies from IgAN patients indicates that they are more susceptible to its effects than patients with other glomerulopathies [12,13]. The immunological activation of mesangial cells may also promote the activation of the renin–angiotensin system and thus contribute to disease progression.

The rationale for using ACEIs to treat IgAN is therefore strong, because they affect the two major factors of CKD progression (systemic and glomerular hypertension, and proteinuria) and block the long series of potentially negative effects of angiotensin II. Unfortunately, the long-term efficacy of ACEIs and ARBs is still uncertain because only one study had a follow-up of >4 years: during the 76-month follow-up of this study by Praga et al. [8], an advantage was found in terms of renal function preservation (steady-state after 60 months), but renal damage progressed thereafter without any further difference between the treated and untreated patients. Consequently, although ACEIs and ARBs (and, more importantly, their combination) are effective, this single therapeutic approach cannot be considered the gold standard therapy for IgAN.



   Are corticosteroids necessary and safe?
Top
 Introduction
 What is the role...
 Are corticosteroids necessary...
Are steroids alone always...
 What should be done...
 References
 
The seven randomized controlled trials of corticosteroids published over the last 20 years [14–21] have shown that steroids are effective in reducing proteinuria and slowing the progression of renal damage. Only Katafuchi et al. [19] reported contradictory results, but the lack of a consistent benefit may have been due to a too-low steroid dose.

The rationale underlying the use of steroids is related to their anti-inflammatory and immunosuppressive effects, which depend on three main mechanisms: a direct effect on gene expression as a result of the binding of glucocorticoid receptors to glucocorticoid-responsive elements, an indirect effect on gene expression through the interactions of glucocorticoid receptors with other transcription factors (NF-{kappa}B) and a glucocorticoid receptor-mediated effect on second-messenger cascades [22].

In 1999, we published the findings of a prospective randomized trial [20] of supportive therapy alone (43 patients) or treatment with 1 g of intravenous methylprednisolone for three consecutive days at the beginning of months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for 6 months (43 patients). The results were striking, particularly after the disappointments of previous therapeutic approaches and general scepticism concerning the use of steroids in IgA nephropathy without nephrotic-range proteinuria—a scepticism that was clearly demonstrated by the fact that it took us 8 years to enrol 86 patients. Nine (21%) of the patients on steroids and 14 (33%) in the control group reached the primary endpoint of a 50% increase in plasma creatinine levels, whereas only one (2%) and nine (21%), respectively reached the primary endpoint of a 100% increase in plasma creatinine during the 5-year follow-up. Renal survival was significantly better in the steroid group in terms of both endpoints (81 vs 64% and 95% vs 74%, improvements of 27 and 28%, respectively: log-rank test P < 0.048 and <0.005).

What was even more striking was the number of patients requiring treatment in order to prevent one event: on the basis of our results, it would be necessary to treat only four patients for 6 months in order to avoid one event over 5 years of follow-up. By comparison, the Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan (RENAAL) and Irbesartan in Diabetic Nephropathy Trial (IDNT) studies [23, 24], which are generally considered as representing major innovative advances in the treatment of nephropathic patients with type 2 diabetes, respectively found that 29 and 16 patients would need to be treated with an ARB for 3 years in order to save one event; and the meta-analysis of Jafar et al. [25] concerning the use of ACEIs for slowing the progression of non-diabetic CKD found that it would be necessary to treat 14 patients for 2 years in order to save one event.

The difference is indeed striking! Furthermore, the results of the cooperate trial [7] showed that, in comparison with an ACEI or ARB alone, nine patients would need to receive the combined therapy for 3 years in order to prevent one event.

Our trial was criticized on three main grounds: (i) the fact that we did not systematically use an ACEI and/or ARB, and so it is impossible to say whether the same results could have been obtained by simply using these drugs in all patients; (ii) concerns about the tolerability and side effects of our steroid course; (iii) scepticism concerning the long-term effects of a treatment regimen lasting only 6 months in patients with such a long life expectancy.

It can be pointed out that there was no difference in the number of hypertensive patients in our two study groups at baseline (14 in the steroid and 15 in the control group) and no differences in blood pressure control between the two groups. As far as the use of ACEIs and/or ARBs is concerned, it must be remembered that the study was started almost 20 years ago, when there was still a fear of using ACEIs in patients with CKD because of the risk of worsening renal function suggested by early experiences with captopril (ARBs were not available at that time). Only six of the 43 patients in each group received an ACEI at baseline (the homogeneous distribution was a matter of chance related to randomization) and, more importantly, although the use of ACEIs gradually increased during the follow-up, the between-group homogeneity was maintained, as they were eventually administered to 19 patients in the steroid group and 17 in the control group.

The beneficial slowing of proteinuria and CKD progression was related to the steroid treatment and not to the use of ACEIs, which univariate and multivariate Cox regression analyses showed had no effect on renal survival. Interestingly, when the reduction in proteinuria over the first 6 months was added to the model as a covariate, it was selected (RR 0.48; 95% CI 0.34–0.69; P < 0.0001) and the beneficial effect of steroid treatment disappeared (P < 0.41), thus suggesting that the effect of steroid treatment may have been due to the decrease in proteinuria levels.

In relation to the possible side effects of our steroid treatment, the total amount of steroids received by the patients was exactly the same as that included in Ponticelli's regimen, which is widely accepted by the nephrological community; furthermore, unlike Ponticelli, we did not use immunosuppressive agents. Although we used nine 1 g boli of methylprednisolone, the oral steroid dose was only 0.5 g/kg on alternate days, and it is well known that steroid toxicity is mainly related to the oral dose. Furthermore, the number of side effects in our trial was as low as that observed with Ponticelli's scheme. Finally, it must be underlined that steroids were used for only 6 months, but the results lasted for many years: only one patient in the steroid group received another 2 months of steroid therapy after 4 years because of an increase in proteinuria.

We have recently published the long-term results of our trial [21]. One (2.3%) of the 43 patients in the steroid group and 13 (30.2%) of the 43 in the control group reached the endpoint of a doubling in baseline plasma creatinine levels after a median follow-up of 7 years, and 10-year renal survival was significantly better in the steroid group (97 vs 53%; log-rank test P = 0.0003). It is also worth pointing out that our steroid scheme was safe both during the short-term and during the 10-year follow-up. We would finally like to underline the fact that steroid therapy improved the prognosis in every histological class: of the seven patients with a severe histological score, the two in the control group progressed to renal insufficiency, whereas the five steroid-treated patients retained stable renal function.

A meta-analysis [26] of six studies including our trial [20] seems to further support the use of corticosteroids in reducing proteinuria and preventing progression to CKD stage 5. Unfortunately, it arbitrarily combined studies with different designs (including non-randomized trials), steroid treatment schedules, end-points and follow-ups.

A very recently published study by Hogg et al. [27] was unable to demonstrate the superiority of prednisone per os or omega-3 fatty acids (O3FA) over placebo in slowing the progression of renal disease (73% of the patients completed 2 years of treatment). Unfortunately, this trial was underpowered with only 14 events overall (estimated GFR <60% of the baseline), affecting only two patients in the prednisone group, eight in the O3FA group and four in the placebo group. We, therefore, agree with the authors that ‘the relative short follow-up period, inequality of baseline Urinary Protein/Creatinine (UP/C) ratios and small number of patients precludes definitive conclusions’.



   Are steroids alone always enough?
Top
 Introduction
 What is the role...
 Are corticosteroids necessary...
 Are steroids alone always...
What should be done...
 References
 
Cytotoxic drugs are possibly useful in progressive IgAN [28], but their use is limited by their serious side effects. The results obtained with cyclosporin-A are disappointing, and those of small trials of mycophenolate mofetil have been conflicting [29–31], with its positive effects seeming to be racially driven (Asian populations), although other trials are currently ongoing.

Patients with rapidly progressive IgA resistant to steroids alone may benefit from steroids in combination with cyclophosphamide and azathioprine, as proposed by Ballardie and Roberts [28], but this schedule seems to be too long and is associated with many important side effects, and so it is of paramount importance to find a safer approach. This is why we designed a randomized controlled trial to test the efficacy of azathioprine added to steroids and full blood pressure control, including an ACEI or an ARB [32]. The very recent study by Yoshikawa et al. [33], although involving a paediatric population, seems to support the efficacy of azathioprine (associated with heparin-warfarin and dipyridamole) added to steroids for 2 years in increasing the disappearance of proteinuria and reducing the percentage of sclerosed glomeruli.



   What should be done in everyday clinical practice?
Top
 Introduction
 What is the role...
 Are corticosteroids necessary...
 Are steroids alone always...
 What should be done...
References
 
Although IgAN has a polymorphic clinical and histological picture, its initial clinical presentation is microscopic haematuria and proteinuria, with or without macroscopic haematuria, in at least 80% of the cases [34]. Proteinuria is the most important urinary abnormality in prognostic terms because large-scale studies have revealed significant differences in renal survival depending on the range of proteinuria [35]: patients with proteinuria levels of >3.5 g/24 h show a loss of 9 ml/min in GFR every year, whereas those with levels of 1–3.5 g/24 h show a loss of 6–7 ml. Other significant prognostic factors of IgAN progression are the duration of proteinuria and the level of proteinuria after 1 year and during follow-up as a whole [21, 36, 37].

In our opinion, treatment should be started as soon as such findings are confirmed without waiting to evaluate the histological score or the progression of CKD. Patients should first be put on antihypertensive treatment in order to reach a blood pressure target of <125–130/75–80 mmHg but >110/70 mmHg [25], depending on proteinuria level, possibly starting with an ACEI or an ARB or both (in the case of persistent proteinuria ≥1 g/24 h); if proteinuria ≥1 g/24 h continues, our steroid scheme should then be added. As pointed out earlier, every year of persistent proteinuria means a loss of nephrons causing a decrease in GFR of 6–7 ml/min, and so it is important to try the scheme without any delay in order to obtain a possibly persistent decrease in proteinuria such as that observed in a large percentage of our treated patients.

What can be done in the case of so-called ‘benign’ IgAN? Unfortunately, there are very few published studies of patients presenting with ‘favourable’ clinical features (i.e. normal renal function, absence of hypertension, and proteinuria of <1 g/24 h), and little is known about their natural history. However, benign features at onset do not always indicate a favourable disease course and so, even in patients with proteinuria of <1 g/24 h (or without proteinuria), careful monitoring over time is essential in order to detect the appearance or an increase in proteinuria or hypertension as soon as possible.

One important and still open question is whether it is useful to treat such patients in an attempt to decrease the risk of developing proteinuria levels to >1 g/24 h and thereby halting or at least slowing down CKD progression. No controlled clinical studies of this possibility have yet been published, but we have designed a randomized controlled trial with the primary aim of testing whether blocking the rennin-angiotensin system (RAS) can decrease the risk of progressive CKD in patients with ‘benign IgAN’ using a single drug class (ACEI or ARB) as a first step, and then combining the two classes whenever proteinuria increases by at least 50% [38].

In conclusion, while waiting for more specific and effective treatments for so-called ‘benign IgAN’, and given the difficulties arising from the polymorphic clinical, laboratory and histological picture of IgAN, we suggest (Table 1) starting with an ACEI or ARB (and then a combination of both) and subsequently adding our 6-month steroid regimen in the case of patients with persistent proteinuria of ≥1 g/24 h. While awaiting the results of our study [32] and other studies, patients with more progressive forms who are resistant to previous treatments (including steroids) could be cautiously treated with the addition of cytotoxic agents.


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  		Table 1. Step-by-step hierarchical approach to treating IgAN on the basis of proteinuria

 
Conflict of interest statement. None declared.



   References
Top
 Introduction
 What is the role...
 Are corticosteroids necessary...
 Are steroids alone always...
 What should be done...
 References
 

  1. Locatelli F, Del Vecchio L, Pozzi C. (2006) IgA glomerulonephritis: beyond angiotensin–converting enzyme inhibitors. Nat Clin Prac Nephrol 2:26–31.
  2. Appel GB and Waldman M. (2006) The IgA nephropathy treatment dilemma. Kidney Int 69:1939–1944.[CrossRef][Web of Science][Medline]
  3. Appel GB. (2006) To treat or not to treat IgA nephropathy? Clin J Am Soc Nephrol 1:347–348.[Medline]
  4. Maschio G, Cagnoli L, Claroni F, et al. (1994) ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. Nephrol Dial Transplant 9:265–269.[Abstract/Free Full Text]
  5. Woo KT, Lau YK, Wong KS, Chiang GSC. (2000) ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. Kidney Int 58:2485–2491.[CrossRef][Web of Science][Medline]
  6. Russo D, Minutolo R, Pisani A, et al. (2001) Coadministration of Losartan and Enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 38:18–25.[Web of Science][Medline]
  7. Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. (2003) Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. Lancet 361:117–124.[CrossRef][Web of Science][Medline]
  8. Praga M, Gutierrez E, Gonzales E, Morales E, Hernandez E. (2003) Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 14:1578–1583.[Abstract/Free Full Text]
  9. Horita Y, Tadokoro M, Taura K, et al. (2004) Low-dose combination therapy with Temocapril and Losartan reduces proteinuria in normotensive patients with immunoglobulin A nephropathy. Hypertens Res 27:963–970.[CrossRef][Web of Science][Medline]
  10. Li PK, Leung CB, Chow KM, et al. (2006) HKVIN Study Group. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis 47:751–760.[CrossRef][Web of Science][Medline]
  11. Egido J. (1996) Vasoactive hormones and renal sclerosis. Kidney Int 49:578–597.[Web of Science][Medline]
  12. Hale GM, Howarth GS, Aarons I, Clarkson AR, Woodroffe AJ. (1989) Quantitation of glomerular angiotensin II receptors in IgA nephropathy. Clin Nephrol 32:5–9.[Web of Science][Medline]
  13. Coppo R, Amore A, Gianoglio B, et al. (1993) Angiotensin II local hyperreactivity in the progression of IgA nephropathy. Am J Kidney Dis 21:593–602.[Web of Science][Medline]
  14. Lai KN, Lai FM, Ho CP, Chan KW. (1986) Corticosteroid therapy in IgA with nephritic syndrome: a long-term controlled trial. Clin Nephrol 26:174–180.[Web of Science][Medline]
  15. Welch TR, Fryer C, Shely E, Witte D, Quinian M. (1992) Double-blind, controlled trial of short-term prednisone therapy in immunoglobulin A glomerulonephritis. J Ped 121:471–477.
  16. Julian BA and Baker C. (1993) Alternate-day prednisone therapy in IgA nephropathy. Preliminary analysis of a prospective, randomized, controlled trial. Contrib Nephrol 104:198–206.[Medline]
  17. Kobayashi Y, Hiki Y, Kokubo T, Horii A, Tateno S. (1996) Steroid therapy during the early stage of progressive IgA nephropathy. Nephron 72:237–242.[Web of Science][Medline]
  18. Shoji T, Nakanishi I, Suzuki A, et al. (2000) Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis 35:194–201.[Web of Science][Medline]
  19. Katafuchi R, Ikeda K, Mizumasa T, et al. (2003) Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy. Am J Kidney Dis 41:972–983.[CrossRef][Web of Science][Medline]
  20. Pozzi C, Bolasco PG, Fogazzi GB, et al. (1999) Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet 353:883–887.[CrossRef][Web of Science][Medline]
  21. Pozzi C, Andrulli S, Del Vecchio L, et al. (2004) Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol 15:157–163.[Abstract/Free Full Text]
  22. Rhen T and Cidlowski JA. (2005) Antiinflammatory action of glucocorticoids – New mechanisms for old drugs. New Engl J Med 353:1711–23.[Free Full Text]
  23. Brenner BM, Cooper ME, de Zeeuw D, et al. (2001) RENAAL Study Investigators: effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869.[Abstract/Free Full Text]
  24. Lewis EJ, Hunsicker LG, Clarke WR, et al. (2001) For the Collaborative Study Group: renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860.[Abstract/Free Full Text]
  25. Jafar TH, Schmid CH, Landa M, et al. (2001) Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Ann Intern Med 135:73–87.[Abstract/Free Full Text]
  26. Samuels JA, Strippoli GF, Craig JC, et al. (2004) Immunosuppressive treatments for immunoglobulin A nephropathy: a meta-analysis of randomized controlled trials. Nephrology 9:177–185.[CrossRef][Medline]
  27. Hogg RJ, Lee J, Nardelli N, et al. (2006) Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 1:467–474.[CrossRef][Medline]
  28. Ballardie FW and Roberts ISD. (2002) Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy. J Am Soc Nephrol 13:142–148.[Abstract/Free Full Text]
  29. Maes BD, Oyen R, Claes K, et al. (2004) Mycophenolate mofetil in IgA nephropathy: results of a 3-year prospective placebo-controlled randomized study. Kidney Int 65:1842–1849.[CrossRef][Web of Science][Medline]
  30. Tang S, Leung JC, Chan LY, et al. (2005) Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int 68:802–12.[CrossRef][Web of Science][Medline]
  31. Frisch G, Lin J, Rosenstock J, et al. (2005) Mycophenolate mofetil (MMF) vs placebo in patients with moderately advanced IgA nephropathy: a double-blind randomized controlled trial. Nephrol Dial Transplant 20:2139–2145.[Abstract/Free Full Text]
  32. Locatelli F, Pozzi C, Del Vecchio L, et al. (1999) Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial. J Nephrol 12:308–311.[Web of Science][Medline]
  33. Yoshikawa N, Honda M, Iijima K, et al. for the Japanese Pediatric IgA Nephropathy Treatment Study Group. (2006) Steroid treatment for severe childhood IgA nephropathy: a randomized, controlled trial. Clin J Am Soc Nephrol 1:511–517.[Medline]
  34. Szeto CC, Lai FM, To KF, et al. (2001) The natural history of immunoglobulin A nephropathy among patients with hematuria and minimal proteinuria. Am J Med 110:434–437.[CrossRef][Web of Science][Medline]
  35. Usui J, Yagamata K, Kai H, et al. (2001) Heterogeneity of prognosis in Adult IgA Nephropathy, especially with mild proteinuria on mild histological features. Intern Med 40:697–702.[Web of Science][Medline]
  36. Coppo R and D'Amico G. (2005) Factors predicting progression of IgA nephropathies. J Nephrol 18:503–512.[Web of Science][Medline]
  37. Deschamps-Latscha B, Witko-Sarsat V, Nguyen-Khoa T, et al. (2004) Early prediction of IgA nephropathy progression: proteinuria and AOOP are strong prognostic markers. Kidney Int 66:1606–12.[CrossRef][Web of Science][Medline]
  38. Pozzi C, Del Vecchio L, Casartelli D, et al. (2006) ACE-inhibitors and angiotensin-II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study. J Nephrol (in press).
Received for publication: 5. 5.06
Accepted in revised form: 31. 7.06


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