Book Review

Treatment of Primary Glomerulonephritis

N Engl J Med 1997; 337:1250-1251October 23, 1997

Article

Treatment of Primary Glomerulonephritis
(Oxford Clinical Nephrology Series.) Edited by Claudio Ponticelli and Richard J. Glassock. 260 pp., illustrated. New York, Oxford University Press, 1997. $110. ISBN: 0-19-262666-3

Renal medicine is largely a disappointing discipline for the practicing physician. Although dialysis and transplantation can nowadays successfully substitute for renal function when kidneys have failed, there are almost no effective treatments for chronic glomerular diseases. Large-scale clinical trials have investigated ways to protect what is left of renal mass after injury or to retard inexorable progression toward renal failure, but there are no well-designed studies with sufficient statistical power concerning the specific treatment of glomerulonephritis. This may be due partly to insufficient knowledge of the mechanism (or mechanisms) of the glomerular injury and partly to the relative rarity of these syndromes. Modern nephrology was born when orderly classification of glomerular diseases was achieved. This classification is based on the pathologic description of the injured glomerulus, and it distinguishes primary forms (not associated with extrarenal manifestations) from secondary forms, which are associated with systemic diseases. The book of Ponticelli and Glassock is an excellent overview of all the efforts to treat primary glomerular diseases.

The opening chapter examines all the aspects of symptomatic or supportive therapy — the measures to correct or attenuate the biochemical imbalance and pathophysiologic disturbances that follow renal damage. In the second chapter, 52 of the book's 260 pages are devoted to an exhaustive and up-to-date review of the clinical pharmacology of drugs that have been used to treat glomerular diseases (or are at an investigational stage). This chapter contains abundant information regarding the side effects of the various drugs, which offers the practicing physician the opportunity to balance the advantages and risks of these treatments. The subsequent chapters summarize the natural history of primary glomerular diseases and the effects of various treatments.

All the chapters are replete with references to small, uncontrolled studies and to larger, controlled clinical trials, although the latter could rarely be considered statistically powerful enough to allow definitive conclusions. The authors make generous use of tables and figures to summarize the results of these studies. Concise algorithms illustrate the authors' suggested plan for a patient affected by a given glomerular disease. As a matter of fact, practical recommendations are what nephrologists look for in a book like this, and the authors fulfill this need.

However, I am not sure that all their recommendations can be taken for granted. Most of them are based on small, uncontrolled clinical trials, and it is difficult to pack together sparse observations in one conclusive statement on the efficacy of a proposed therapy. In fact, small studies generally have positive results, but when therapeutic hypotheses are tested on a large scale they often fail to show a definitive benefit. Curiously, there is a contradiction in the book regarding the use of meta-analysis in nephrology. Ponticelli and Passerini criticize the application of this method to studies on membranous nephropathy, noting that pooling the results of studies with different designs, populations, and forms of therapy is an intrinsic limit of the meta-analysis. Yet in another chapter, Glassock states that meta-analysis of trials in IgA nephropathy supports the beneficial effect of steroid therapy on reduction of proteinuria.

One has the general impression that this book is a collection of conscientiously documented chapters but lacks internal consistency and a unifying overview of the mechanisms of damage, and therefore of the therapeutic approach. It is probably time to look at the glomerular diseases with a different perspective. It appears that minimal lesions respond well to steroids; active inflammatory lesions, such as those in crescenteric forms, are often sensitive to immunosuppressive drugs; and when sclerosis is the prevailing pathologic feature, there is very little hope of avoiding progression and renal failure, whatever the treatment. While we are waiting for such an approach to be consecrated in print, this book should be considered a good, up-to-date source of information and references on the treatment of glomerular diseases and should be consulted critically by all those facing these problems in the daily practice of nephrology.

Giuseppe Remuzzi, M.D.
Negri Bergamo Laboratories, 24100 Bergamo, Italy