Waldenström's macroglobulinaemia and acute renal failure: isoosmolal non-ionic contrast medium is not an absolute contraindication

Roberto Scarpioni1, Luciano Cristinelli1, Pietro Quaretti2, Davide Imberti3 and Pietro Cavallotti3

1 Department of Nephrology and Dialysis 2 Department of Radiology 3 Department of Internal Medicine III, Piacenza AUSL Hospital, Piacenza, Italy

Sir,

We read with interest the paper of Wong et al. [1] about acute tubular necrosis in Waldenström's macroglobulinaemia (WM) with hyperviscosity syndrome. We would like to point to another aspect of acute renal failure (ARF) and WM namely the use of contrast media (CM). The use of contrast media is reported to confer a high risk to the renal survival of patients with paraproteinaemias, especially when associated with renal failure. However, in the literature there is no report on the use of low osmolality contrast media (LOCM) in patients with WM and renal failure.

Case.

A 70-year-old man was admitted for renal failure with severe hypertension. The latter was diagnosed in 1980, but no investigations were done at that time. On admission the patient had light headache, without neurologic signs; physical examination revealed a vascular ‘bruit’ over the left flank.

Drug-related hypertension, cerebrovascular disease, or a cardiac cause of hypertension were excluded. Laboratory studies revealed renal failure (serum creatinine 2.4 mg/dl, urea 65 mg/dl, creatinine clearance 28 ml/min) with moderate anaemia and a monoclonal component in the {gamma} region on serum electrophoresis, an IgM M-component with {kappa} light chains on immunoelectrophoresis with a high serum IgM concentration (1.130 mg/dl, normal values 40–230 mg/dl), and {kappa} light chains on urine immunoelectrophoresis. Fundoscopic examination demonstrated arteriolar narrowing and arterio-venous crossing but no papilledoema.

An abdominal echography showed a small right kidney without parenchymal border and compensatory left renal hypertrophy: left renal artery stenosis (RAS) was suggested by doppler duplex (RADD) examination and renal scintigraphy. A bone marrow biopsy was performed and showed a feature of WM. X-ray examination did not reveal osteolytic lesions. The moderately elevated IgM concentration (5 times normal) excluded a hyperviscosity syndrome. Clinical, laboratory and radiographic data were not in favour of rapid disease progression. Therefore, a specific WM chemotherapy was not undertaken.

Because of uncontrolled hypertension and worsening of renal failure (serum creatinine up to 4.2 mg/dl) a renal angiography was performed, confirming ostia left renal artery stenosis by more than 70% and complete absence of visualization of the right kidney. Percutaneous transluminal angioplasty was performed with Palmaz 154 stent positioning. The LOCM used was iodixanol, at a total dose of 50 ml.

Serum creatinine determination in the following days showed progressive worsening of renal function with an improvement in blood pressure control and a reduction in anti-hypertensive drug therapy.

At present, 12 months after hospital dismission, serum creatinine is stable at 2.8 mg/dl and blood pressure is well controlled. A repeat RADD examination excluded re-stenosis of the left renal artery.

Comment.

This case highlights the potential hazardous use of non-ionic LOCM iodixanol in ARF, and WM, in presence of a single kidney with RAS and hypertensive crisis. This constellation has never been reported in literature. Both acute and chronic renal failure are less frequent in WM than in multiple myeloma (MM) but renal involvement in WM is generally chronic. It usually depends on the circulating level of serum IgM that may induce a hyperviscosity syndrome, especially when serum monoclonal IgM levels are greater than 3 g/dl. Since in our patient the IgM concentration was only five times that of the normal level, this hypothesis was unlikely. In WM renal failure may be rarely associated with cryoglobulinaemia or with primary amylodosis. Both were excluded in this case.

CM nephropathy of paraproteinaemias was first reported by Bartels [2] in 1954 but in the literature there has been only one paper referring to ARF in WM, in association with the use of the high osmolality CM ditrazoate for pyelography [3]. In a retrospective study reviewing patients with MM who had received CM, the incidence of CM-induced renal failure was only 0.6–1.25% suggesting as predominant risk factors of ARF, hypercalcaemia, dehydration, infection and the presence of Bence Jones protein, rather than CM alone. The currently used LOCM do not appear to precipitate Bence Jones protein in vitro [4], which is present in 80–90% of WM patients, in much lower amounts than those seen in MM, while ionic high osmolality contrast media may enhance aggregation of Tamm-Horsfall (T-H) protein, an important factor in the development of renal failure in patients with MM and paraproteinaemias [5]. There is no report in the literature on the use of non-ionic CM and on T-H protein in WM or in paraproteinaemias. Although the use of CM has been largely treated for MM, this was not the case for other paraproteinaemias that may differ as to the primary risk for kidney function. No such study has been published since 1992 and the only report on the use of CM in WM refers to ionic high osmolality contrast media [3].

The property of contrast media as a precipitating factor for Bence Jones protein is probably related to ionic CM. The safety of non-ionic LOCM in patients with WM and Bence Jones proteinuria has never been specifically addressed in any clinical or experimental studies. Furthermore, the lower the dose of CM infused, the safer it appears to be in patients with renal insufficiency: although no study specifically referred to intra-arterial CM use, which should exert a stronger ischaemic insult on kidney, we were able to utilize a very low CM dose, less than 50 ml in total.

In conclusion, despite multiple risk factors for renal survival (acute renal failure, severe hypertension, WM with Bence Jones proteinuria, single kidney and intra-arterial use of CM), the present patient showed improvement of residual renal function at 1 year follow up, with satisfactory blood pressure control allowing a reduction of the number of hypotensive drugs. The adequate hydration before and after CM examination, the continuation of calcium-blocker therapy and the use of low doses of iso-osmolal non-ionic CM (iodixanol) may have contributed to this success.

The use of non-contrast-media procedures should be favoured whenever possible. However, our experience shows that in a patient affected by WM with ARF, RAS and one single kidney, if necessary, CM studies with low doses of non ionic, dimeric LOCM (iodixanol) can be performed, considering that in elderly patients with paraproteinaemias it is important to identify other unrelated causes of renal impairment such as renovascular disease. Nevertheless larger studies of the use of LOCM in WM with renal impairment are requested, waiting for new non-iodinated contrast agents.

References

  1. Wong PN, Mak SK, Lo KY, Tong G, Wong A. Acute tubular necrosis in a patient with Waldenström's macroglobulinaemia and hyperviscosity syndrome. Nephrol Dial Transplant2000; 15: 1684–1687[Free Full Text]
  2. Bartels ED, Brun GC, Gammeltoft A, Gjorub PA. Acute anuria following intravenous pyelography in patients with myelomatosis. Acta Med Scand1954; 150: 297–302[ISI][Medline]
  3. Matsumoto J, Yasaka T, Ohya I, Ohtani H. Acute renal failure in primary macroglobulinemia with small molecule IgM. Arch Int Med1985; 145: 929–931[Abstract]
  4. Lasser EC, Lang JH, Zawadzki ZA. Contrast media-myeloma protein precipitates in urography. JAMA1996; 198: 945–947
  5. Huang ZQ, Kirk KA, Connel KG, Sanders PW. Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall glycoprotein to promote heterotypic aggregation. J Clin Invest1993; 92: 2975–2983[ISI][Medline]




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