The Official Patient's Sourcebook on Lupus (9 page)

Biopsy:
The removal and examination, usually microscopic, of tissue from the living body, performed to establish precise diagnosis. [EU]

Catheter:
A tubular, flexible, surgical instrument for withdrawing fluids from (or introducing fluids into) a cavity of the body, especially one for

introduction into the bladder through the urethra for the withdraw of urine.

[EU]

Cyclophosphamide:
Precursor of an alkylating nitrogen mustard

antineoplastic and immunosuppressive agent that must be activated in the

liver to form the active aldophosphamide. It is used in the treatment of

lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in

defleecing sheep. Cyclophosphamide may also cause sterility, birth defects,

mutations, and cancer. [NIH]

Glomerulonephritis:
A variety of nephritis characterized by inflammation of the capillary loops in the glomeruli of the kidney. It occurs in acute,

subacute, and chronic forms and may be secondary to haemolytic

streptococcal infection. Evidence also supports possible immune or

autoimmune mechanisms. [EU]

Infertility:
The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an

offspring. [NIH]

Inflammation:
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is

42 Lupus Nephritis

usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]

Infusion:
The therapeutic introduction of a fluid other than blood, as saline solution, solution, into a vein. [EU]

Intermittent:
Occurring at separated intervals; having periods of cessation of activity. [EU]

Lupus:
A form of cutaneous tuberculosis. It is seen predominantly in

women and typically involves the nasal, buccal, and conjunctival mucosa.

[NIH]

Nephritis:
Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial

renal tissue. [EU]

Nephropathy:
Disease of the kidneys. [EU]

Nephrotic:
Pertaining to, resembling, or caused by nephrosis. [EU]

Prednisone:
A synthetic anti-inflammatory glucocorticoid derived from

cortisone. It is biologically inert and converted to prednisolone in the liver.

[NIH]

Pulse:
The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of

the heart as it contracts. [NIH]

Rectal:
Pertaining to the rectum (= distal portion of the large intestine). [EU]

Sigmoidoscopy:
Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH]

Systemic:
Pertaining to or affecting the body as a whole. [EU]

43

ABOUT PART II

In Part II, we introduce you to additional resources and advanced research

on lupus nephritis. All too often, patients who conduct their own research

are overwhelmed by the difficulty in finding and organizing information.

The purpose of the following chapters is to provide you an organized and

structured format to help you find additional information resources on lupus

nephritis. In Part II, as in Part I, our objective is not to interpret the latest advances on lupus nephritis or render an opinion. Rather, our goal is to give

you access to original research and to increase your awareness of sources

you may not have already considered. In this way, you will come across the

advanced materials often referred to in pamphlets, books, or other general

works. Once again, some of this material is technical in nature, so

consultation with a professional familiar with lupus nephritis is suggested.

Studies 45

CHAPTER 4. STUDIES ON LUPUS NEPHRITIS

Overview

Every year, academic studies are published on lupus nephritis or related

conditions. Broadly speaking, there are two types of studies. The first are

peer reviewed. Generally, the content of these studies has been reviewed by

scientists or physicians. Peer-reviewed studies are typically published in

scientific journals and are usually available at medical libraries. The second type of studies is non-peer reviewed. These works include summary articles

that do not use or report scientific results. These often appear in the popular press, newsletters, or similar periodicals.

In this chapter, we will show you how to locate peer-reviewed references

and studies on lupus nephritis. We will begin by discussing research that has

been summarized and is free to view by the public via the Internet. We then

show you how to generate a bibliography on lupus nephritis and teach you

how to keep current on new studies as they are published or undertaken by

the scientific community.

The Combined Health Information Database

The Combined Health Information Database summarizes studies across

numerous federal agencies. To limit your investigation to research studies

and lupus nephritis, you will need to use the advanced search options. First,

go to
http://chid.nih.gov/index.html
. From there, select the “Detailed

Search” option (or go directly to that page with the following hyperlink:

http://chid.nih.gov/detail/detail.html
). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may

refine your search by.” Select the dates and language you prefer, and the

46 Lupus Nephritis

format option “Journal Article.” At the top of the search form, select the

number of records you would like to see (we recommend 100) and check the

box to display “whole records.” We recommend that you type in “lupus

nephritis” (or synonyms) into the “For these words:” box. Consider using the

option “anywhere in record” to make your search as broad as possible. If

you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is a sample of what you can expect from this type of search:

·
Advances in the Treatment of Lupus Nephritis

Source: in Coggins, C.H.; Hancock, E.W., Eds. Annual Review of

Medicine: Selected Topics in the Clinical Sciences, Volume 45. Palo Alto,

CA: Annual Reviews Inc. 2001. p. 63-78.

Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O.

Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax: (415) 855-9815.

Price: $47. ISBN: 0824305450.

Summary: Systemic lupus erythematosus (SLE) is an autoimmune

disease that leads to the formation and deposition of immune complexes

throughout the body, which are pathogenic (causing disease) for SLE.

Different forms of glomerulonephritis (inflammation of the filtering units

of the kidney) can occur in patients with SLE and can contribute

significantly to the associated morbidity (illness and complications) and,

ultimately, mortality (death) from the disease. Over the past two decades,

there have been significant strides in the understanding of the disease

and in treatments that attempt to control the formation and deposition of

anti-DNA auto-antibodies and immune complexes, as well as the

subsequent inflammatory cascade mediated through various cellular and

humoral pathways leading to progressive renal (kidney) damage and end

stage renal disease (ESRD). This article reviews the current

understanding of the pathogenesis and treatment of lupus nephritis in its

various stages and discusses the experimental and human data regarding

some of the potential newer forms of therapy. The authors discuss data

regarding the use of steroids, azathioprine, cyclophosphamide,

cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis,

LJP 394, flaxseed oil, bindarit, anti-CD-40 ligand, and CRLA41g. The

authors conclude that the long term morbidity and mortality for patients

with lupus nephritis (LN) has improved markedly over the past two

decades. This is due in part to the addition of newer adjunctive therapies

to control blood pressure and intraglomerular pressure, reduce

proteinuria (protein in the urine), and manage hyperlipidemia (high

levels of fats in the blood). 89 references.

Studies 47

·
Treatment of Lupus Nephritis

Source: Seminars in Nephrology. 20(3): 265-276. May 2000.

Contact: Available from W.B. Saunders Company. Periodicals

Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-

2452.

Summary: Patients with lupus nephritis pose a therapeutic challenge and

stimulate investigation of innovative treatment strategies. This article

reviews those current and potential strategies that may optimize

management of lupus nephritis. The clinical presentations of lupus

nephritis can vary from asymptomatic hematuria (blood in the urine) or

proteinuria (protein in the urine) to acute nephritic or nephrotic

syndromes and from rapidly progressive glomerulonephritis to insidious

chronic renal insufficiency. Although patient survival and renal function

outcomes have improved over the last 4 decades, contemporary

immunosuppressive regimens are not consistently effective and often

require extended courses (resulting in negative drug effects and toxicity).

Several strategies are under investigation to induce remissions more

rapidly and to reduce the risk of long courses of cytotoxic drug therapy.

The combination of pulse methylprednisolone and pulse

cyclophosphamide may be more effective than pulse cyclophosphamide

alone for patients with relatively severe proliferative lupus nephritis. A

particularly vigorous strategy employs immunoablative

cyclophosphamide, with or without stem cell rescue. Several studies of

sequential immunosuppressive therapy are in progress. It is anticipated

that long term toxicities can be lessened by substituting various

maintenance agents (e.g., azathioprine or mycophenolate mofetil) after

initial cyclophosphamide therapy has induced a renal responses.

Innovative approaches (e.g., costimulatory blockade) offer the hope of

more effective treatments without the risks of contemporary regimens. 2

figures. 2 tables. 88 references.

·
Progress in the Treatment of Proliferative Lupus Nephritis

Source: Current Opinion in Nephrology and Hypertension. 9(2): 107-115.

2000.

Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600,

Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-

2400. Website: www.currentopinion.com.

Summary: Lupus nephritis (kidney inflammation associated with

systemic lupus erythematosus, or SLE) is often well developed at the time

of diagnosis. This article reviews progress in the treatment of

proliferative lupus nephritis. High dose corticosteroids are universally

48 Lupus Nephritis

accepted as the initial approach to the control of severe inflammation in

the kidney. Long term disease control and the minimization of iatrogenic

(physician caused) risk usually require adjunctive therapies that target

the more fundamental immunoregulatory disturbances of lymphoid cells.

Of the available cytotoxic drugs, cyclophosphamide is currently among

the most effective, although it cannot be considered ideal in terms of

efficacy or toxicity. New prospects for the treatment of proliferative lupus

nephritis include novel immunosuppressive agents (e.g., mycophenolate,

cyclosporine, fludarabine), combination chemotherapy (e.g.,

cyclophosphamide plus fludarabine), and sequential chemotherapy (e.g.,

cyclophosphamide followed by azathioprine), immunological

reconstitution using intensive cytoreductive chemotherapy (with or

without stem cell rescue), and co stimulatory molecule inhibition. Gene

therapy remains an attractive prospect, but its feasibility clearly depends

on the further definition of lupus promoting genes and the availability of

methods to establish stable expression of disease corrective genes in the

appropriate lymphoid cells. 3 figures. 83 references.

·
Efficacy of Mycophenolate Mofetil in Patients with Diffuse

Proliferative Lupus Nephritis

Source: New England Journal of Medicine. 343(16): 1156-1162. October

19, 2000.

Summary: The combination of cyclophosphamide and prednisolone is

effective for the treatment of severe lupus nephritis (kidney inflammation

associated with systemic lupus erythematosus or SLE) but has serious

adverse effects. This article reports on a study that investigated the

efficacy of mycophenolate mofetil in patients (n = 42) with proliferative

lupus nephritis. The authors compared the efficacy and side effects of a

regimen of prednisolone and mycophenolate mofetil given for 12 months

(group 1) with those of a regimen of prednisolone and cyclophosphamide

given for 6 months, followed by prednisolone and azathioprine for 6

months (group 2). Of the patients in Group 1 (n = 21), 81 percent had a