A Retrospective Analysis of the Natural History of Primary IgA Nephropathy Worldwide F. PAOLO SCHENA, mi, /ta/y
The worldwide medical literature was reviewed to determine whether the prevalence, clinical presentation, and immunohistologic findings of primary IgA nephropathy were related to geographic areas. A total of 68 reports containing detailed clinical histories and laboratory fmdings were analyzed. The selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Analysis of the data showed that IgA nephropathy is more frequent in the Asian area than in Australia, Europe, and North America. The male/female ratio indicates that males are more likely to be affected by the disease, particularly in the second and third decade of life. The appearance of the disease is characterized by microscopic hematuria and mild proteinuria in Asians, whereas gross hematuria is more frequent in American and European patients. At the time of renal biopsy, fixed microscopic hematuria is detected in a high percentage of patients in Asia and Europe, whereas macroscopic hematuria is more frequent in American patients. Mild renal lesions occur more frequently in Asian patients, while severe renal lesions and a high frequency of immunoglobulin and complement deposits are present in American and European patients. Differences encountered in this retrospective analysis may be influenced by two important factors: (1) the absence of urinalysis screening programs in the schools of Europe and North America, and (2) the different approaches to renal biopsy in the eastern and western parts of the world. Due to the high rate of renal insufficiency and end-stage kidney disease in European and North American patients with IgA nephropathy, it is recommended that a program of urinalysis screening in schools and an appropriate renal biopsy policy be adopted in the western areas of the world.
From the University of Bari, Polyclinic, Ban, Italy. This study was partly supported by Grants 87-222.04 and 88-644.04 from the Consiglio Nazionale delle Ricerche, Rome, and by grants 87-5050 and 88-6088 from the Minister0 delta Pubblica Istruzlone. Rome, Italy. Requests for reprints should be addressed to Professor F. Paolo Schena. Polyclinic, 70124 Bari. Italy. Manuscript submltted October 10. 1989, and accepted In revised form March 7. 1990.
C
onsiderable knowledge has accumulated concerning the clinical and immunopathologic abnormalities in primary IgA nephropathy. The cause of this glomerulonephritis, which has considerable potential to progress to end-stage kidney disease, remains obscure. After the first description by Berger and Hinglais [l] in 1968, many reports of large series of patients were published. It is now clear that IgA nephropathy is the most common form of glomerulonephritis in the world, but conflicting evidence concerning the frequency of the disease and immunologic abnormalities has been reported [2-41. To assess whether these disparities may be due to geographic locale or other unknown factors, I reviewed detailed clinical and immunopathologic aspects of the disease from studies published in the last 20 years. MATERIALS AND METHODS Criteria Reports published between 1968 and 1988 were examined. In all the reports, the patients fulfilled the following diagnostic criteria for IgA nephropathy: hematuria and mesangial deposits of IgA at renal biopsy. Systemic lupus erythematosus, SchGnlein-Henoch purpura, and hepatic disease were excluded on the basis of the clinical history, the results of examination, and the laboratory findings. Reports with insufficient details for clinical assessment and those that described cases that were reported previously by the same investigators were excluded from the analysis. For analysis of the data, the selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Definitions Microscopic hematuria was defined as the presence or persistence of traces of blood in the urine during the course of the disease. Patients with macroscopic hematuria included subjects with one or more episodes of gross hematuria. The latter group, therefore, included both patients who presented with a single episode of macroscopic hematuria at the time the disease appeared, followed by continuous or intermittent microscopic hematuria, and subjects with recurrent episodes of gross hematuria associated with bacterial or viral infection. The nephritic syndrome was characterized by hematuria, proteinuria, azotemia, oliguria, and hypertension. The nephrotic syndrome was defined as a proteinuria greater than 3.0 g/day, serum albumin less than 3.0 g/dL, and edema. Renal function was defined as normal when the serum creatinine level was 1.5 mg/dL or less and the creatinine clearance more than 80 ml/minute. Decreased renal function was characterized by a serum creatinine level more than 1.5 mg/dL and a creatinine clearance less than 80 ml/minute. Uremic patients August
1990
The American
Journal
of Medicine
Volume
89
209
PRIMARY
IgA NEPHROPATHY
/ SCHENA 1
disease among all renal biopsy samples studied by the immunofluorescent technique, IgA nephropathy was 40%’ more frequent in Asia (29.2%) than in Australia (12%), Europe (10.7%, p
The worldwide medical literature was reviewed to determine whether the prevalence, clinical presentation, and immunohistologic findings of primary IgA nephropathy were related to geographic areas. A total of 68 reports containing detailed clinical histories and laboratory fmdings were analyzed. The selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Analysis of the data showed that IgA nephropathy is more frequent in the Asian area than in Australia, Europe, and North America. The male/female ratio indicates that males are more likely to be affected by the disease, particularly in the second and third decade of life. The appearance of the disease is characterized by microscopic hematuria and mild proteinuria in Asians, whereas gross hematuria is more frequent in American and European patients. At the time of renal biopsy, fixed microscopic hematuria is detected in a high percentage of patients in Asia and Europe, whereas macroscopic hematuria is more frequent in American patients. Mild renal lesions occur more frequently in Asian patients, while severe renal lesions and a high frequency of immunoglobulin and complement deposits are present in American and European patients. Differences encountered in this retrospective analysis may be influenced by two important factors: (1) the absence of urinalysis screening programs in the schools of Europe and North America, and (2) the different approaches to renal biopsy in the eastern and western parts of the world. Due to the high rate of renal insufficiency and end-stage kidney disease in European and North American patients with IgA nephropathy, it is recommended that a program of urinalysis screening in schools and an appropriate renal biopsy policy be adopted in the western areas of the world.
From the University of Bari, Polyclinic, Ban, Italy. This study was partly supported by Grants 87-222.04 and 88-644.04 from the Consiglio Nazionale delle Ricerche, Rome, and by grants 87-5050 and 88-6088 from the Minister0 delta Pubblica Istruzlone. Rome, Italy. Requests for reprints should be addressed to Professor F. Paolo Schena. Polyclinic, 70124 Bari. Italy. Manuscript submltted October 10. 1989, and accepted In revised form March 7. 1990.
C
onsiderable knowledge has accumulated concerning the clinical and immunopathologic abnormalities in primary IgA nephropathy. The cause of this glomerulonephritis, which has considerable potential to progress to end-stage kidney disease, remains obscure. After the first description by Berger and Hinglais [l] in 1968, many reports of large series of patients were published. It is now clear that IgA nephropathy is the most common form of glomerulonephritis in the world, but conflicting evidence concerning the frequency of the disease and immunologic abnormalities has been reported [2-41. To assess whether these disparities may be due to geographic locale or other unknown factors, I reviewed detailed clinical and immunopathologic aspects of the disease from studies published in the last 20 years. MATERIALS AND METHODS Criteria Reports published between 1968 and 1988 were examined. In all the reports, the patients fulfilled the following diagnostic criteria for IgA nephropathy: hematuria and mesangial deposits of IgA at renal biopsy. Systemic lupus erythematosus, SchGnlein-Henoch purpura, and hepatic disease were excluded on the basis of the clinical history, the results of examination, and the laboratory findings. Reports with insufficient details for clinical assessment and those that described cases that were reported previously by the same investigators were excluded from the analysis. For analysis of the data, the selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Definitions Microscopic hematuria was defined as the presence or persistence of traces of blood in the urine during the course of the disease. Patients with macroscopic hematuria included subjects with one or more episodes of gross hematuria. The latter group, therefore, included both patients who presented with a single episode of macroscopic hematuria at the time the disease appeared, followed by continuous or intermittent microscopic hematuria, and subjects with recurrent episodes of gross hematuria associated with bacterial or viral infection. The nephritic syndrome was characterized by hematuria, proteinuria, azotemia, oliguria, and hypertension. The nephrotic syndrome was defined as a proteinuria greater than 3.0 g/day, serum albumin less than 3.0 g/dL, and edema. Renal function was defined as normal when the serum creatinine level was 1.5 mg/dL or less and the creatinine clearance more than 80 ml/minute. Decreased renal function was characterized by a serum creatinine level more than 1.5 mg/dL and a creatinine clearance less than 80 ml/minute. Uremic patients August
1990
The American
Journal
of Medicine
Volume
89
209
PRIMARY
IgA NEPHROPATHY
/ SCHENA 1
disease among all renal biopsy samples studied by the immunofluorescent technique, IgA nephropathy was 40%’ more frequent in Asia (29.2%) than in Australia (12%), Europe (10.7%, p
