IgA nephropathy: in Hong Kong

K K L Ho 何繼良

HK Pract 2001;23:453-456

Summary

IgA nephropathy has been recognised to be the most common primary glomerulonephritis worldwide and in Hong Kong. It has variable clinical presentations but incidental finding of microscopic haematuria is most common. The nephropathy is not an entirely benign disease. Initial presentation with microscopic haematuria and low-grade proteinuria may deteriorate into advanced renal failure. The prognosis of the nephropathy is associated with various clinical risk factors. Co-existing hypertension seems to be the most significant risk factor associated with progressive renal failure. Control of hypertension is the most important treatment to improve the prognosis. Treatment with angiotensin converting enzyme inhibitors and perhaps angiotensin-II receptor antagonists appear to be beneficial. Corticosteroid and immunosuppressive agents can also be considered in more advance disease to prevent the progression to end stage renal failure.

摘要

無論在全世界或者在香港，免疫球蛋白腎病（IgA Nephropathy）都是最常見的一種原發性腎小球腎炎，它臨床表現多樣，多為偶然發現的鏡下血尿。它的病情不一定全為良性，有些早期鏡下血尿和輕微蛋白尿可能演變為末期腎衰竭。腎病的預後和多種危險因素有關，共存的高血壓是腎衰竭最重要的危險因素，而控制血壓可改善預後。

使用血管緊張素轉化抑制劑或者血管緊張素—II感受器頡抗劑治療免疫球蛋白A腎病可以有效控制病情。皮質類固醇和免疫抑制劑則用於較嚴重病例以防發展成為末期腎衰竭。

Introduction

IgA nephropathy was first reported by Berger and Hinglais as Berger's disease in 1968.¹ The nephropathy is the most common primary glomerulonephritis worldwide^2,3 and represents the most common condition encountered in diagnostic renal biopsy examination accounting for 35% of all primary glomerulonephritis in Hong Kong.³

Presentation

IgA nephropathy commonly manifests in young adults and the incidence peaks between 25 to 34 years of age in Hong Kong.^4,5 The nephropathy is occasionally diagnosed in older patients when a renal biopsy is performed for the investigation of increasing proteinuria and/or renal impairment. It is the second most common glomerulonephritis of children in Hong Kong.⁵ IgA nephropathy has diverse clinical presentations ranging from asymptomatic microscopic haematuria and/or proteinuria to advanced renal impairment. The most common renal manifestation is isolated microscopic haematuria accounting for 25% of the cases.^6-8 It is usually detected incidentally during a routine health check-up by urinalysis. Other presentations are macroscopic haematuria (19%) commonly associated with a history of upper respiratory tract infection, and, significant proteinuria. More than half of the patients present with a degree of proteinuria higher than 1gm/day. Nephrotic syndrome and renal impairment are occasionally found in patients at presentation. Patients with IgA nephropathy and their first-degree relatives seem to have an increased prevalence of hypertension.^9-11 The presence of pre-existing hypertension in patients with IgA nephropathy without renal impairment is not uncommon, especially in those with a positive family history of hypertension.

Some aspects of the nephropathy in Asian patients differ from patients from Western countries. The incidence of the nephropathy is higher in Asian than Caucasian populations.⁵ The male predilection reported in Caucasian is not observed in Asian populations. The male to female ratio is 0.94 in Hong Kong similar to Japan and Singapore.^12,13 However, the cause of a different sex ratio is unclear.

There seems to be an association between hepatitis B and the nephropathy in Hong Kong. The percentage of patients with IgA nephropathy and coincidental hepatitis B surface antigenaemia is 17.2%, which is significantly higher than 9.5% in the general population.¹⁴ Hepatitis B antigenaemia has been suggested to play a pathogenic role in the nephropathy and is associated with the development of progressive renal impairment.

The natural history

IgA nephropathy has diverse clinical presentations and variable outcomes.¹⁵ It was once believed the nephropathy behaved like benign recurrent haematuria. However, clinical data have shown that up to 30% of patients progress to end stage renal failure after 15 to 20 years of clinical manifestation of the disease.^7,8,16,17 Even those patients with only mild haematuria, proteinuria of 0.4gm/day or less, and normal blood pressure, previously claimed to have good prognoses are not free from developing complications of the disease.¹⁸ Up to 44% of these patients progress to develop significant proteinuria (>1gm/day), hypertension, and/or renal impairment in a median follow up of seven years. Forty-two percent of patients have persistent abnormal urinalysis. Only 14% of patients have complete resolution of haematuria. Therefore, patients presenting with microscopic haematuria should be followed-up by a family physician, after the exclusion of other causes of haematuria, to detect changes of the condition early in the clinical course. Renal biopsy should be considered when there is increasing proteinuria and/or renal impairment.

Various clinical factors have been suggested to be associated with increased risk of progressive renal impairment in IgA nephropathy.^7,16,17 The general consensus is that co-existing hypertension is the most important indicator of a poor prognosis. Patients with poorly controlled hypertension are usually associated with rapid deterioration of renal function. Significant proteinuria (>1gm/day), impaired renal function, and high pathohistologic scoring of renal biopsy at presentation are also important clinical factors associated with a higher risk of renal failure.^8,18-23 The prevalence of hepatitis B surface antigenaemia is higher in patients with IgA nephropathy in Hong Kong. These patients with hepatitis B virus-associated IgA nephropathies can develop slowly progressive renal impairment. A positive family history of hypertension and hyperlipidaemia are independent risk factors of renal impairment.^9,24-28

Treatment

The pathogenesis of the disease remains unclear and there is no disease-specific treatment for the nephropathy. Our aim is to delay, even if unable to halt, the progression of the disease to advanced renal failure. Controlling high systemic blood pressure is the most important treatment for both early and advanced stages of the disease.²⁹ Patients with blood pressure controlled below 130/70mmHg were shown to have stable renal function compared with significant reduction of creatinine clearance in patients with higher blood pressure 140/85mmHg. Various kinds of antihypertensive drugs have been used. The anti-proteinuric effects of angiotensin converting enzyme inhibitors (ACEI), angiotensin-II receptor antagonists (AT II), and certain calcium channel blockers seem to be comparable, however, some studies have shown that ACEI and AT II have a greater anti-proteinuric effect than calcium channel blockers in various kinds of nephropathy. Whether or not their greater anti-proteinuric effect confers better protection of renal function in all kinds of nephropathies remains to be confirmed by further studies. ACEI has also been shown to preserve renal function both in hypertensive and normotensive nephritic patients.³⁰ Therefore, ACEI seems to have an additional benefit of protecting the kidney function other than by lowering the systemic blood pressure alone. Captopril has been shown to have potentially beneficial effects on diminishing proteinuria as well as mesangial lesions in experimental models of IgA nephropathy whereas other types of antihypertensive drugs do not seem to have a similar effect.³¹ Further studies are required to prove the effect is beneficial to human beings. Dry cough remains a problematic side effect of ACEI in the Chinese population of Hong Kong. AT II has much less side effect of dry cough, but there is not at present much clinical data to show AT II can delay renal impairment in humans.

Corticosteroid and immunosuppressive agents, when used in the early stage of the disease, are useful in treating a subgroup of nephritic patients with impaired renal function and significant proteinuria. These patients have renal histopathology of segmental necrotising lesion with crescent formation. Early treatment can lower the incidence of progressive renal failure.^32-34 Omega-3 fatty acids have been shown to be effective in preserving renal function in patients with IgA nephropathy and mild renal impairment. Higher dose (EPA 3.76g and DHA 2.94g) of fatty acids, however, does not seem to give additional renal protective effect compared with low-dose fatty acids (EPA 1.88g and DHA 1.47g).³⁵ 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) has been shown to have antiproteinuric effects in patients with IgA nephropathy.³⁶ Statins have also been shown to reduce the extent of glomerulosclerosis in experimental models of progressive renal disease. It remains to be studied whether statins can protect patients with IgA nephropathy from progressive renal failure. Other agents and procedures have also been used in the treatment for IgA nephropathy. However, there is no convincing evidence that these agents are useful in reducing the incidence of progressive renal failure in most patients with IgA nephropathy. These agents include antiplatelet drugs, anticoagulants, prophylactic antibiotics, and tonsillectomy.^37,38

In conclusion, IgA nephropathy is a heterogeneous disease with many different risk factors. Patients with hypertension, significant proteinuria, impaired renal function, and high pathohistologic scoring of renal biopsy at presentation are at increased risk of renal impairment. Family physicians have a special role in early detection of the disease in the general population when presented with microscopic haematuria. Simple dipstick analysis and microscopic study of dysmorphic red blood cells in urine is most useful. Identification and early referral of patients at risk of progressive renal failure are beneficial for further management. Regular follow up and good control of systemic blood pressure remain the most important treatments for the prevention of progression to renal failure.