Remission of proteinuria improves prognosis in IgA nephropathy.

Proteinuria has been shown to be an adverse prognostic factor in IgA nephropathy. The benefit of achieving a partial remission of proteinuria, however, has not been well described. We studied 542 patients with biopsy-proven primary IgA nephropathy in the Toronto Glomerulonephritis Registry and found that glomerular filtration rate (GFR) declined at -0.38 +/- 0.61 ml/min per 1.73 m2/mo overall, with 30% of subjects reaching end-stage renal disease. Multivariate analysis revealed that proteinuria during follow-up was the most important predictor of the rate of GFR decline. Among the 171 patients with <1 g/d of sustained proteinuria, the rate of decline was 90% slower than the mean rate. The rate of decline increased with the amount of proteinuria, such that those with sustained proteinuria >3 g/d (n = 121) lost renal function 25-fold faster than those with <1 g/d. Patients who presented with > or =3 g/d who achieved a partial remission (<1 g/d) had a similar course to patients who had < or =1 g/d throughout, and fared far better than patients who never achieved remission. These results underscore the relationship between proteinuria and prognosis in IgA nephropathy and establish the importance of remission.

[1]  G. Remuzzi,et al.  Cellular responses to protein overload: key event in renal disease progression , 2004, Current opinion in nephrology and hypertension.

[2]  G. Remuzzi,et al.  Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN). , 1998, Kidney international.

[3]  D. Cattran,et al.  Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[4]  E. Bergstralh,et al.  Proteinuria patterns and their association with subsequent end-stage renal disease in IgA nephropathy. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  Eun Sun Lee,et al.  Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee's glomerular grading system. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[6]  C. Schmid,et al.  Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data. , 2001, Annals of internal medicine.

[7]  G. D'Amico,et al.  Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. , 2004, Seminars in nephrology.

[8]  G. Remuzzi,et al.  Protein Overload-Induced NF-κB Activation in Proximal Tubular Cells Requires H2O2 through a PKC-Dependent Pathway , 2002 .

[9]  P. Finne,et al.  Factors associated with progression of IgA nephropathy are related to renal function--a model for estimating risk of progression in mild disease. , 2002, Clinical nephrology.

[10]  David Roth,et al.  A simplified equation to predict glomerular filtration rate from serum creatinine , 2000 .

[11]  Masaki Kobayashi,et al.  Natural history and risk factors for immunoglobulin a nephropathy in Japan , 1997 .

[12]  J. Scholey,et al.  Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. , 2005, Journal of the American Society of Nephrology : JASN.

[13]  N. Perico,et al.  ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy. , 1999, American journal of physiology. Renal physiology.

[14]  K. Chow,et al.  Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[15]  K. Chow,et al.  Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[16]  A. Koyama,et al.  Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. , 1997, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[17]  K Doqi,et al.  clinical practice guidelines for chronic kidney disease : evaluation, classification, and stratification , 2002 .

[18]  M. Wehrmann,et al.  IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients. , 1990, American journal of nephrology.

[19]  H. Morita,et al.  Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. , 2003, Lancet.

[20]  F. Lai,et al.  The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria. , 2001, The American journal of medicine.

[21]  R. Poveda,et al.  Goodpasture syndrome during the course of a Schönlein-Henoch purpura. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[22]  D. Tritchler,et al.  Albumin activates ERK via EGF receptor in human renal epithelial cells. , 2005, Journal of the American Society of Nephrology : JASN.

[23]  F. Locatelli,et al.  Effect of the Angiotensin-Converting–Enzyme Inhibitor Benazepril on the Progression of Chronic Renal Insufficiency , 1996 .

[24]  H. Shigematsu,et al.  IgA nephropathy: prognostic significance of proteinuria and histological alterations. , 1983, Nephron.

[25]  G. Remuzzi,et al.  Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules? , 1990, Kidney international.

[26]  F. Lai,et al.  Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives. , 2002, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[27]  A. Jardine,et al.  A tricontinental view of IgA nephropathy. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  É. Renoult,et al.  IgA nephropathy: prognostic classification of end-stage renal failure. L'Association des Néphrologues de l'Est. , 1997 .

[29]  G. D'Amico,et al.  Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  Regional program for the study of glomerulonephritis. Central Committee of the Toronto Glomerulonephritis Registry. , 1981, Canadian Medical Association journal.

[31]  A. Pisani,et al.  Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. , 1999, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[32]  K. Chan,et al.  Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo. , 2003, The Journal of clinical investigation.

[33]  Cockcroft Dw,et al.  Prediction of Creatinine Clearance from Serum Creatinine , 1976 .

[34]  G. D'Amico,et al.  The commonest glomerulonephritis in the world: IgA nephropathy. , 1987, The Quarterly journal of medicine.

[35]  Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia) , 1997, Lancet.

[36]  L. Ibels,et al.  IgA Nephropathy: Analysis of the Natural History, Important Factors in the Progression of Renal Disease, and a Review of the Literature , 1994, Medicine.

[37]  Giuseppe Remuzzi,et al.  Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria , 1999, The Lancet.

[38]  Tsuyoshi Watanabe,et al.  The Product of Duration and Amount of Proteinuria (Proteinuria Index) Is a Possible Marker for Glomerular and Tubulointerstitial Damage in IgA Nephropathy , 2002, Nephron.

[39]  E. Morales,et al.  Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. , 2003, Journal of the American Society of Nephrology : JASN.

[40]  D. Cattran,et al.  Predicting progression in IgA nephropathy. , 2001, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[41]  E. Jones,et al.  Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. , 2000, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[42]  C. Ponticelli,et al.  Prognostic indicators in idiopathic IgA mesangial nephropathy. , 1986, The Quarterly journal of medicine.

[43]  H. Bucht,et al.  Deterioration rate in hypertensive IgA nephropathy: comparison of a converting enzyme inhibitor and beta-blocking agents. , 1991, Nephron.

[44]  G. Remuzzi,et al.  Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kappa B activation. , 1998, Kidney international.

[45]  Christopher H Schmid,et al.  Progression of Chronic Kidney Disease: The Role of Blood Pressure Control, Proteinuria, and Angiotensin-Converting Enzyme Inhibition: A Patient-Level Meta-Analysis , 2003, Annals of Internal Medicine.

[46]  G. Remuzzi,et al.  Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy. , 1991, Kidney international.

[47]  J. Scholey,et al.  Idiopathic membranous nephropathy: definition and relevance of a partial remission. , 2004, Kidney international.

[48]  Kdoqi Disclaimer K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[49]  M. Nagata,et al.  Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features. , 2001, Internal medicine.

[50]  K. Wong,et al.  ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis. , 2000, Kidney international.

[51]  H. Morita,et al.  RETRACTED: Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial , 2003, The Lancet.

[52]  G. Remuzzi,et al.  Protein overload-induced NF-kappaB activation in proximal tubular cells requires H(2)O(2) through a PKC-dependent pathway. , 2002, Journal of the American Society of Nephrology : JASN.

[53]  E. Bergstralh,et al.  Predicting renal outcome in IgA nephropathy. , 1997, Journal of the American Society of Nephrology : JASN.

[54]  F. Locatelli,et al.  Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. , 1996, The New England journal of medicine.

[55]  G. Maschio,et al.  ACE inhibition reduces proteinuria in normotensive patients with IgA nephropathy: a multicentre, randomized, placebo-controlled study. , 1994, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[56]  M. Haas,et al.  Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. , 1997, American journal of kidney diseases : the official journal of the National Kidney Foundation.