A CASE WITH ACUTE RENAL FAILURE COMPLICATED BY WALDENSTRÖM'S MACROGLOBULINEMIA AND CRYOGLOBULINEMIA

Abstract

We encountered a 53-year-old man associated with acute renal failure caused by Waldenström's macroglobulinemia and type I cryoglobulinemia. Treatment with prednisolone and cyclophosphamide induced a rapid recovery from acute renal failure. Renal histology revealed endocapillary proliferation and lobular formation with scattered subendothelial, amorphous and periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries which were positive for IgM on immunofluorescence study. Although the exact mechanism for pathophysiology of acute renal failure remains unknown, treatment with prednisolone and cyclophosphamide could induce a rapid recovery from acute renal failure accompanied by Waldenström's macroglobulinemia and type I cryoglobulinemia.

• acute renal failure
• cryoglobulin
• cyclophosphamide
• prednisolone
• Waldenström's macroglobulinemia

INTRODUCTION

Waldenström's macroglobulinemia (WM) is characterized by monoclonal proliferation of lymphoproliferative cells that produce monoclonal IgM. Characteristic renal pathological lesions of WM are amyloidosis or lesions with subendothelial deposition of amorphous periodic acid-Schiff (PAS)-positive materials in the glomerular capillaries [[1]]. But with multiple myeloma, acute renal failure (ARF) associated with WM occurs quite rarely.

This paper presents a rare case of ARF associated WM, which was successfully treated with prednisolone and cyclophosphamide.

CASE REPORT

The patient was a 53-year-old male admitted to this hospital on October 13, 1997 owing to pretibial edema. Non-nephrotic proteinuria had been noted since 1993. The patient had been well until eight months earlier, when Raynaud's phenomenon and leg ulcers were noted. At another hospital, he had diagnosed as WM based on monoclonal elevation of IgM and the presence of urinary IgM. On April 17, 1997, interferon −2b was administered as treatment for one month and in conjunction with CHOP therapy (cyclophosphamide 500 mg, vincristine 1.5 mg, adriamycin 60 mg, prednisone 60 mg) on May 30 for 5 days. At the start of that treatment serum creatinine level was 1.0 mg/dL.

On admission, blood pressure and pulse rate were 170/100 mmHg and 84 per minute with regular rhythm, respectively. Pretibial edema and healed ulcer lesions in the left leg were noted. Urine was 3(+) for protein and 2(+) for occult blood. Urinary excretion of protein exceeded 5 g/24 h. Urine sediment disclosed 20 erythrocytes per high-power field with the absence of cast. Blood laboratory data were as follows: hemoglobin, 8.5 g/dL, creatinine, 3.0 mg/dL, blood urea nitrogen, 51.0 mg/dL, total protein, 5.4 g/dL, albumin, 2.4 g/dL, IgG, 914 mg/dL, IgM, 1730 mg/dL, and IgA, 84 mg/dL. IgM was present in the urine and serum and cryoglobulin (type I monoclonal) was detected in the serum.

The clinical course of the patient is shown in Figure1. Serum creatinine level rapidly increased to 5.4 mg/dL on October 21 and prednisolone (60 mg/day) and cyclophosphamide (50 mg/day) administration was started on the following day. Hemodialysis was started on October 25 and continued for three days in consideration of exaggerated edema and the progress of azotemia (creatinine 7.0 mg/dL). As shown in Figure1, prednisolone and cyclophosphamide brought about rapid decline in serum creatinine level to 2.8 mg/dL over 10 days but had no effect on proteinuria (data not shown). Prednisolone was tapered to 10 mg/day and cyclophosphamide was discontinued but serum creatinine level remained essentially the same. Renal biopsy was made on November 13, at which time serum creatinine level was 1.9 mg/dL.

Figure 1. Time courses of serum levels of creatinine (solid line) and IgM (dotted line) during the period of prednisolone and cyclophosphamide administration.

Light microscopy demonstrated global sclerosis in 6 of 19 glomeruli. Endocapillary proliferation and lobular formation with scattered subendo thelial, amorphous, PAS-positive deposits could be seen in 13 glomeruli. Representative glomerulus showed scattered subendothelial, amorphous and PAS-positive deposits in glomerular capillaries, positive for IgM on immunofluorescence (IF) study, with endocapillary proliferation. No significant damage of the tubuli could be detected. IgG, IgM, C₃ were stained along glomerular capillaries on IF. Electron dense deposits on electron microscopy could be seen in the subendothelial space.

DISCUSSION

Amorphous PAS-positive subendothelial deposits in the glomerular capillaries is the characteristic renal lesion in WM. Numerous deposits sometimes occlude the glomerelar capillary lumen, thus forming thrombi. This lesion with variable degree of proteinuria and normal or slightly altered renal function was found in 6 cases in the series of 16 autopsy and biopsy cases [[2]]. Two of the 6 cases had cryoglobulinemia, in which renal histology revealed slight glomerular cell proliferation. It has been also demonstrated that nearly 10% of monoclonal IgM in WM has been shown to be cryoglobulins, which consist of type I monoclonal cryoglobulinemia and type II mixed cryoglobulinemia with monoclonal IgM [[3]]. In addition to PAS-positive deposits in the glomerular capillaries, endocapillary proliferation with the formation of double contours, as also noted in membranoproliferative glomerulonephritis, is often observed in such case [[1]].

Acute renal failure associated with WM occurs quite rarely. To our knowledge, there are only two case reports, one in which ARF developed during severe dehydration [[4]] and the other followed pyelography [[5]]. Argani and Kipkie noted the deposition of proteinaceous materials in glomerular capillaries and showed these deposited substances to have the histochemical features of macromolecular protein detected in serum [[4]]. Severe dehydra-tion would thus appear to possibly cause the deposition of monoclonal IgM in glomerular capillaries, resulting in ARF. Matsumoto et al suggest that in ARF following pyelography the small-molecule IgM-chain contrast medium complex may possibly be toxic to renal tissue [[5]].

In the present case, the exact mechanism for acute renal failure was unclear because renal biopsy could not be performed in the onset of ARF. Hypotension and exposure to nephrotoxic substances could not be detected as possible causes. In renal biopsy specimen obtained following recovery of ARF, no tubular injury was observed, but endocapillary proliferation and lobular formation with amorphous PAS-positive deposits in the glomerular capillaries, which was consistent with IgM deposits on IF, were noted. However, it can be speculated that the endocapillary proliferation and the precipitation of monoclonal IgM in glomerular capillaries may quite likely predispose the occlusion of capillaries with consequently reduced glomerular filtration. Since ARF due to rapid protein precipitation has been reported in cryoglobulinemia following exposure to cold melieu [[5]], the precipitation of monoclonal IgM in glomerular capillaries may quite likely predispose the occlusion of capillaries, with consequently reducing glomerular filtration.

Prednisolone and chlorambucil in a patient with WM have been shown to bring about the rapid remission of the nephrotic syndrome along with the disappearance of dense, PAS-positively stained subendothelial deposits in the glomeruli in a short period of time [[7]]. The action of these drugs in the present case may have been expressed through the same mechanisms.