Rationales for treating IgA nephropathies.

An outline is given of the pathophysiology of IgA nephropathy (IgA) in order to emphasize the role of eicosanoids, angiotensin II, and reactive oxygen species. ACE inhibitors and early corticosteroid usage are prime therapies. Tonsillectomy is to be considered, certainly for individual cases. It is logical that other components of a cocktail could be (i) thromboxane antagonists, (ii) leukotriene antagonists, or (iii) PAF antagonist. In theory there should be benefit from antioxidants. Fish oils have not come up to expectation. PDGF aptamers look promising for the prevention of mesangial cell proliferation. Heparins are not used in the way that they could be. Various other agents could help reduce decline.

Ways of treating IgA nephropathies.

SUMMARY: Treatment options for IgA nephropathy (IgAN) must take into consideration the pathophysiology, namely the role of eicosanoids, angiotensin II and monocyte-macrophages releasing reactive oxygen species (ROS). Angiotensin converting enzyme inhibitors and early corticosteroid usage are prime therapies. Tonsillectomy should be considered. Other components of a therapeutic cocktail could be; (a) thromboxane antogonist, (b) leukotriene antagonist, (c) platelet activating factor antagonist, (d) an anti-oxidant and (e) an anti-fibrotic agent like pentoxyfylline. In the new millenium, there will be focus on anti-proliferative measures like platelets dependent growth factor aptamers. For unusual cases with rapid progression, the use of FK-506 or mycophenolate mofetil can be considered.

Antioxidants in the prevention of renal disease.

In view of the role of oxidative processes in inflicting damage that leads to glomerulosclerosis and renal medullary interstitial fibrosis, more attention could be paid to the use of antioxidant food constituents and the usage of drugs with recognized antioxidant potential. In any case atherosclerosis is an important component of chronic renal diseases. There is a wide choice of foods and drugs that could confer benefit. Supplementation with vitamins E and C, use of soy protein diets and drinking green tea could be sufficient to confer remarkable improvements.

Thromboxanes in glomerulonephritis: what about therapy?

A detailed consideration of how thromboxanes are implicated in glomerulonephritis is followed by a summary of how they have been used successfully in experimental and clinical situations. Most human studies have been short-term only.

Modulatory proteins and processes in alliance with immune cells, mediators, and extracellular proteins in renal interstitial fibrosis.

A synopsis of the many aspects and factors that contribute to renal tubulo-interstitial fibrosis is presented. The role of fibrogenic cytokines and the conversion of fibroblasts to myofibroblasts are described. It is emphasized that oxygen radicals cause fibroblasts to generate collagen. The properties of those accessory modulatory proteins that affect the behavior of cells in the interstitium are considered and how matrix for ensuing fibrosis is laid down. Understanding the extracellular matrix proteins and these modulatory proteins is important because their behavior can now be modified by means of antisense oligonucleotides.

Can pentoxifylline prevent renal disease?

The characteristics of pentoxifylline(Trental) suggest that it is an ideal agent to be used as adjunct in the therapy of chronic proliferative glomerulonephritides. Theoretical considerations suggest that pentoxifylline should also protect against and even ameliorate tubulo-interstitial fibrosis of affected kidneys.

Alternative therapies for vasculitis and proliferative nephritides: the role of cyclic AMP elevating agents.

Cytoprotection by E-prostaglandins, working by elevation of intracellular cyclic AMP, is a natural physiological mechanism. When agents that elevate cAMP are used in pharmacological regimens they have potent anti-inflammatory effects that could be used to good effect as adjuncts for the control of vasculitides/nephritides.