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Semin Arthritis Rheum. 2004 Dec;34(3):593-601.
Intravenous immunoglobulin and the kidney--a two-edged sword.

Orbach H, Tishler M, Shoenfeld Y.

Department of Medicine B'Wolfram Medical Center, Holon, Israel.

OBJECTIVES: To review the literature on the use and efficacy of intravenous immunoglobulin (IVIG) in glomerulonephritis and to evaluate the nephrotoxic effect of IVIG. METHODS: A structured literature search of articles published on the efficacy of IVIG in the treatment of nephritis between 1985 and 2003 was conducted. All articles dealing with lupus nephritis, IgA nephropathy, Henoch Schonlein purpura, antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis, primary membranous glomerulonephritis, and primary chronic nephritis were reviewed. The same literature search was conducted for the nephrotoxic effects of IVIG. Two groups of patients were defined: (a) a group of patients with IVIG nephrotoxic effect published as case reports, and (b) a group of patients whose data were collected by the Food and Drug Administration (FDA). All existing data of both groups were pooled and compared.

RESULTS: One hundred six patients with lupus nephritis were treated with IVIG. In most reports proteinuria, nephrotic syndrome, and values of creatinine clearance were improved. In 3 cases improvement in World Health Organization (WHO) class was noted, and in 2 cases a reduction of immune deposits was demonstrated. In the other forms of autoimmune nephropathy, although the number of reported cases was small, improvement was noted in most patients. Thirty-two reports entailing 78 patients with IVIG-induced nephrotoxicity were found and their data were compared with those of 88 patients reported to the FDA. No specific differences were noted between the 2 groups of patients, as their age and indications for using IVIG were similar. Most of the patients who developed renal toxicity (72% in the literature and 90% in the FDA group) received sucrose -containing IVIG products. A high percentage of patients (31% in the literature and 40% in the FDA group) required hemodialysis. Mortality occurred in 10 and 15%, respectively. Renal histology done in a minority of the cases demonstrated vacuolization and swelling of the proximal tubules consistent with osmotic injury.

CONCLUSIONS: On one hand, there are encouraging reports on the efficacy of IVIG in different types of glomerulonephritis (mainly lupus nephritis) resistant to conventional therapy, but the exact success rate and clinical indications remain undetermined. On the other hand, IVIG and the kidney is a two-edged sword, since nephrotoxicity can be a serious rare complication of IVIG therapy. Products containing sucrose as a stabilizer are mainly associated with such injury through the mechanism of osmotic nephrosis. Preexisting renal disease, volume depletion, and old age are risk factors for such toxicity.

 
1:Jpn J Infect Dis. 2004 Oct;57(5):S17-8.  
 
Intravenous immunoglobulin (IVIg) therapy in MPO-ANCA related polyangiitis with rapidly progressive glomerulonephritis in Japan.
Muso E, Ito-Ihara T A, Suzuki K.
Division of Nephrology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
For 30 myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) related rapidly progressive glomerulonephritis patients (male 17, female 13, average age of 68 +/- 11.8 years old), intravenous immunoglobulin (IVIg) (400 mg/kg/day) was administered for 5 consecutive days before or along with conventional immunosuppressive therapy in Japan. Twenty patients were treated with IVIg before the start or newly increase of conventional therapy and evaluated the independent effect of this therapy. In these patients, just after IVIg, significant decrease of CRP from 8.61 +/- 5.77 to 5.47 +/- 4.50 mg/dl (P < 0.001) was noted with improvement of elevated serum creatinine in 12 out of 19 patients (63%). In the analysis of the overall outcome of 30 patients, at 3 months after IVIg and following conventional therapy, no patients showed renal death except 4 for whom hemodialysis had been started before IVIg. At 6 months, renal survival rate were 92% (newly renal death 2 out of 26) and 2 patients died due to cerebral bleeding (survival rate was 93%). No fatal infection was noted. IVIg might be the potent inducible therapy which can be promoted before the beginning of conventional immunosuppressant treatment for relatively aged and lower immunopotent MPO-ANCA patients in Japan.
PMID: 15507757 [PubMed - indexed for MEDLINE]
 
Nippon Jinzo Gakkai Shi. 2004 Feb;46(2):79-83
[Successful treatment of severe ANCA-associated RPGN with high-dose IVIg therapy]
Gomada M, Akamatsu A.
Division of Nephrology, Ehime Prefectural Central Hospital, Ehime, Japan.

We report a case of anti-neutrophil cytoplasmic antibody(ANCA)-associated rapid progressive glomerulonephritis (RPGN) that was treated with intravenous immunoglobulin (IVIg) therapy. A 37-year-old woman was admitted to our hospital because of a low-grade fever, general malaise, and a poor appetite. At the time of admission, her renal function had severely deteriorated (serum creatinine level 9.5 mg/dl; mean Ccr 3.3 ml/min) and she had severe anemia (Hb 6.6 g/dl). An immunological examination revealed the presence of ANCA-associated RPGN. A biopsy confirmed a diagnosis of pauci-immune-type necrotizing crescentic glomerulonephritis. After initial treatment with steroid pulse therapy (methylprednisolone, 1,000 mg/day x 3 days), her general condition deteriorated and two sessions of hemodialysis were required. On the 10th hospital day, a high dose of immunoglobulin was administered intravenously (IVIg 400 mg/kg/day x 5 days). This therapy immediately improved her general condition and lowered her serum titer of MPO-ANCA anti-neutrophil cytoplasmic antibody and her serum creatinine level. After two IVIg treatments, her MPO-ANCA titer returned to a normal level and her serum creatinine level improved from 9.5 mg/dl to 3.3 mg/dl. A second biopsy confirmed clinical improvement. These findings suggest that IVIg therapy is effective for cases of ANCA-associated glomerulonephritis that are difficult to treat using conventional immunosuppressive therapy.
 


PMID: 15058108 [PubMed - indexed for MEDLINE]

 

 

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