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Renal involvement in plasma cell dyscrasias, immunoglobulin-based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias 

Renal involvement in plasma cell dyscrasias, immunoglobulin-based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias

Renal involvement in plasma cell dyscrasias, immunoglobulin-based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias

P Ronco

, F Bridoux

, and G Touchard



Chapter reviewed July 2012—minor changes made.

Updated on 26 Nov 2011. The previous version of this content can be found here.
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Plasma cell dyscrasias are characterized by uncontrolled proliferation of a single clone of B cells which is responsible for the secretion of a monoclonal immunoglobulin (Ig) or Ig subunit that can become deposited in tissues. They can cause a wide range of renal diseases.

Light-chain amyloidosis—renal presentation is usually with proteinuria, often progressing to nephrotic syndrome. Progressive decline in renal function usually occurs, leading finally to endstage renal failure. Diagnosis is made by the detection of monoclonal gammopathy in serum and/or urine (90% of cases) in combination with biopsy evidence of amyloid- forming light chain deposits. Chemotherapy with oral mephalan plus dexamethasone should be considered as first line treatment.

Myeloma—renal failure is found at presentation in 20% of patients, occurs in 50% at some time, and is most commonly caused by cast nephropathy, diagnosis of which relies on the detection of a urinary monoclonal light chain, with renal biopsy typically showing ‘fractured’ casts. Chemotherapy, e.g. high-dose dexamethasone, combined with various drugs including bortezomib, and /or alkylating agents, and/or thalidomide.

Light-chain, light- and heavy-chain, and heavy-chain deposition disease—collectively known as monoclonal Ig deposition diseases, present with proteinuria and renal failure. Diagnosis is by renal biopsy which reveals nodular glomerulosclerosis, monotypic light- and/or heavy-chain deposits along glomerular and tubular basement membranes (by immunofluorescence), and nonfibrillar granular electron-dense deposits (by electron microscopy). Patients with myeloma (45% of cases) are treated with conventional chemotherapy or high-dose therapy followed by autologous stem cell transplantation in selected cases.

Fibrillary glomerulonephritis and immunotactoid glomerulopathy—usual presentation is with the nephrotic syndrome, microscopic haematuria, and hypertension. Diagnosis is by renal biopsy when electron microscopy reveals (respectively) fibrils (solid, diameter 12–22 nm, randomly arranged) or microtubules (hollow, diameter 10–60 nm, sometimes in parallel arrays). Cases associated with chronic lymphocytic leukaemia or lymphoma may respond to chemotherapy.

Cryoglobulinaemia—type II (‘essential mixed’), which involves a monoclonal IgM with rheumatoid factor activity and a polyclonal IgG, may present with proteinuria, haematuria, hypertension, and gradually declining renal function, or with an acute nephritic picture. It should be suspected in the presence of an IgM rheumatoid factor and low complement C4, and confirmed by the finding of a cryoglobulin. It is often associated with hepatitis C. Renal biopsy typically reveals membranoproliferative glomerulonephritis with massive subendothelial deposits. The best treatment is uncertain, but it may involve antiviral agents and/or immunosuppression.

Tumour lysis syndrome—a life-threatening metabolic emergency that occurs in patients with haemopathies with high cell turnover, e.g. Burkitt’s lymphoma and acute leukaemia, mostly at the onset of chemotherapy and/or radiation therapy. Prevention is by vigorous hydration with 0.9% saline before treatment with the addition of allopurinol (in low-risk cases) or the recombinant modified urate oxidase rasburicase (in high-risk cases). Treatment is by saline diuresis (if possible), rasburicase, and haemodialysis (if required).


Plasma cell dyscrasias are characterized by uncontrolled proliferation of a single clone of B cells, usually with plasma cell differentiation, which is responsible for the secretion of a monoclonal immunoglobulin (Ig) or Ig subunit that can become deposited in tissues. The range of renal diseases in which it is recognized that there is deposition or precipitation of Ig-related material has expanded dramatically in recent years.

These conditions can be classified into two categories on the basis of their ultrastructural appearances (Table Those with organized deposits include diseases with crystal formation, mainly myeloma cast nephropathy; diseases with fibril formation, mainly light-chain amyloidosis; and diseases with microtubule formation, including cryoglobulinaemia kidney and immunotactoid/microtubular glomerulonephritis (also called GOMMID for glomerulonephritis with organized microtubular monoclonal Ig deposits). A second category of diseases is characterized by the presence of nonorganized granular electron-dense deposits made of light and/or heavy chains along the basement membranes of many tissues, most importantly the kidney. First described by Randall and associates, these are referred to as monoclonal Ig deposition diseases (MIDD). More recently, glomerular diseases with amorphous monoclonal Ig deposits distinct from Randall-type MIDD have been described. It is now well established that the spectrum of plasma cell dyscrasia-related renal complications is due to intrinsic properties of the monoclonal component.

Table Pathological classification of diseases with tissue deposition or precipitation of monoclonal Ig-related material


Nonorganized (granular)




MIDD (Randall-type)


Myeloma cast nephropathy

Light-chain amyloidosis

Cryoglobulinaemia kidney


Non-Randall-type proliferative GN

Fanconi’s syndrome

Nonamyloid fibrillary GN

Immunotactoid GN/GOMMID


Waldenström’s macroglobulinaemia



GN, glomerulonephritis; GOMMID, glomerulonephritis with organized microtubular monoclonal Ig deposits; LCDD, LHCDD, HCDD, light-chain, light- and heavy-chain, heavy-chain deposition disease; MIDD, monoclonal immunoglobulin deposition disease.

Except for myeloma cast nephropathy, diagnosis relies on careful analysis of a biopsy specimen taken from the kidney, which should systematically include immunohistochemical studies with specific antibodies and also electron microscopy in all ambiguous cases. Since most of these patients will develop renal failure, it is essential to identify the underlying plasma cell dyscrasia because appropriate treatment may halt the extension of visceral deposits, and even induce their regression. Except in patients with myeloma cast nephropathy, who usually present with a high-mass myeloma, ‘malignancy’ more often results from life-threatening visceral deposits than from the Ig-secreting clone itself.

Renal involvement in Ig light-chain amyloidosis

Definition and epidemiology

Amyloidosis is a general term for a family of diseases defined by morphological criteria and characterized by deposition in extracellular spaces of a proteinaceous material that stains with Congo red and is metachromatic. Amyloid deposits are composed of a felt-like array of 10-nm-wide rigid linear aggregated fibrils of indefinite length with a β‎-pleated sheet configuration. They occur in a variety of conditions including Alzheimer’s disease and other neurodegenerative disorders, tumoural and inflammatory diseases, and plasma cell dyscrasias. The various types of amyloidosis differ essentially by the nature of the precursor protein that yields the main component of fibrils, and are classified accordingly (see Chapter 12.12.3 for further discussion).

Light-chain amyloidosis has become the most frequent form of amyloidosis with renal involvement. Amyloid deposits are found in approximately 10% of myeloma patients, their prevalence reaching 20% in those with pure light-chain myeloma (Fig.

Fig. Light-chain amyloidosis. (a) Amyloid deposits in a renal glomerulus. Masson’s trichrome stain, magnification ×312. (b) Apple-green/yellow dichroism under polarized light. Congo red stain, magnification ×312. (c) Immunofluorescence with anti-λ‎ antibody. Note glomerular and arteriolar deposits. Magnification ×312.

Light-chain amyloidosis. (a) Amyloid deposits in a renal glomerulus. Masson’s trichrome stain, magnification ×312. (b) Apple-green/yellow dichroism under polarized light. Congo red stain, magnification ×312. (c) Immunofluorescence with anti-λ‎ antibody. Note glomerular and arteriolar deposits. Magnification ×312.

(From Béatrice Mougenot’s personal collection.)

Clinical presentation

The main clinical features of light-chain amyloidosis at presentation are fatigue (62%) and weight loss (52%), followed by purpura (15%), pain (5%), and gross bleeding (3%). Hepatomegaly is found in 24% of patients, and macroglossia in 9%. A palpable spleen and lymphadenopathy can also be found.

Proteinuria is the usual symptom of renal amyloidosis, detected in 55% of patients at presentation and often progressing to a severe nephrotic syndrome, which can be complicated by renal vein thrombosis. Haematuria is uncommon, and when present should prompt examination for a bleeding lesion of the urinary tract. Progressive decline in renal function usually occurs, leading finally to endstage renal failure. In those rare patients in whom renal tubulointerstitial deposits predominate, renal failure may progress without a nephrotic stage, and in some of these patients renal tubular dysfunction may be the presenting problem, including Fanconi’s syndrome, renal tubular acidosis, or even nephrogenic diabetes insipidus. Hypertension is uncommon but may develop concomitantly with renal failure. The kidneys may be of normal size or large, even when renal function is impaired.

Systemic light-chain amyloidosis can infiltrate almost any organ (except the brain) and thus be responsible for a wide variety of clinical manifestations. It frequently involves the tongue, gastrointestinal tract, peripheral nervous system, carpal tunnel, heart, and skin. Purpuric macules in the periorbital region are very typical of light-chain amyloidosis.


Light-chain amyloidosis should be suspected when the clinical manifestations described above are associated with a monoclonal component in the serum or urine. Light-chain amyloidosis is always the result of the proliferation of a plasma cell clone; 56% of patients have an increased number of plasma cells in the bone marrow, and 15% have true myeloma. Monoclonal light chains are detected by immunoelectrophoresis of urine in around 73% of cases, with the λ‎ isotype being twice as frequent as the κ‎ isotype. An over-representation of the Vλ‎6 subgroup has been found in AL amyloidosis with renal involvement. With the use of more sensitive techniques such as immunofixation, a monoclonal Ig is found in the serum and/or the urine in nearly 90% of patients, but still not in all of them. The recent development of a sensitive nephelometric immunoassay for circulating free Ig light chains has been an important advance in the management of AL amyloidosis, allowing detection of abnormal serum free light chain levels in 98% of patients and reliable monitoring of response to chemotherapy.

However, it is important to recognize that detection of monoclonal gammopathy is insufficient for the diagnosis of AL amyloidosis, which should be established in all cases by taking a biopsy specimen from a superficial organ, including skin, salivary glands, and gum, or by aspiration biopsy of abdominal fat. These biopsies should be performed before biopsies of rectal mucosa (which should include vessels of the submucosa where amyloid deposits usually start) and/or of kidney, because of the risk of bleeding complications due to factor X deficiency or amyloid infiltration of vascular walls. After Congo red staining, amyloid deposits appear faintly red and show characteristic apple-green birefringence under polarized light. Congo red staining may be falsely negative if tissue sections are less than 5 µm in thickness. Metachromasia is also observed with crystal violet, which stains the deposits red. In the kidney, the earliest lesions are located in the mesangium, along the glomerular basement membrane, and in the blood vessels. Because there are specific diagnostic and therapeutic strategies depending on the type of protein deposited within tissues, immunofluorescence with specific antisera including anti-κ‎ and anti-λ‎ light chains should be performed routinely. When pathological confirmation of AL type cannot be obtained, genetic studies should be performed to exclude systemic hereditary amyloidosis caused by mutations in the genes encoding transthyretin, fibrinogen A α‎-chain, lysozyme or apolipoprotein A-I or A-II, all of which are frequently associated with renal involvement. New techniques, that combine specific sampling by laser microdissection followed by tandem mass spectrometry-based proteomic analysis, may help to identify the nature of amyloid deposits in paraffin-embedded tissue biopsy samples, with a great sensitivity and specificity.


Light-chain amyloidosis is a wasting disease with a mean survival of only 6 to 15 months in untreated patients. Cardiac involvement is a main prognostic factor, accounting for 30% of deaths. The aim of treatment is to suppress production of amyloidogenic free light chain with acceptable toxicity. Due to the lack of comparative clinical trials, treatment of AL amyloidosis is debated. Low-dose chemotherapy (oral melphalan and prednisone) was extensively used in the 1990s with modest increase in median survival (up to 18 months). Improved results have been obtained with intermediate-dose regimens, such as vincristine, doxorubicin, and dexamethasone (VAD), or, more recently, oral melphalan plus dexamethasone. These regimens, which induce rapid and higher rates of haematological response, have been shown to increase median survival to 40 to 50 months, with limited treatment-related mortality. Intensive therapy, i.e. high-dose intravenous melphalan followed by autologous stem cell transplantation, has been extensively used in recent years, resulting in complete clonal response in up to 40% of cases and median survival of 4.6 years. However, such intensive therapy is associated with high morbidity and treatment-related mortality, ranging from 12% in experienced centres to more than 40% in multicentre series. It is therefore limited to selected patients, usually on the basis of the following criteria: aged under 70 years, one or two organs involved, glomerular filtration rate above 50 ml/min, and absence of advanced amyloid cardiopathy. In a randomized controlled trial that enrolled 100 patients with systemic AL amyloidosis, oral melphalan plus dexamethasone resulted in improved overall survival compared to high-dose chemotherapy followed by autologous stem cell transplantation, suggesting that intensive therapy should be offered only to those refractory to conventional chemotherapy. The introduction of new agents used for the treatment of multiple myeloma, including thalidomide, lenalidomide and (particularly) bortezomib, in association with high dose dexamethasone, with or without an alkylating agent, is likely to result in increased survival by inducing high hematological (> 70%) and organ response rates.

Results of chemotherapy in amyloidosis are difficult to document because organ response is often delayed and there is no easy way to measure the amount of amyloid present. Resolution of the nephrotic syndrome does not necessarily reflect the disappearance of amyloid deposits, and the progressive deposition of amyloid can occur despite improved clinical and laboratory findings. Scintigraphy after the injection of 123I-labelled serum amyloid P (SAP) may be helpful for monitoring the extent of systemic amyloidosis, but it is available only in a limited number of centres (see Chapter 12.12.3). The effects of chemotherapy are better evaluated by serial nephelometric measurements of serum free light chains. When remission of the underlying plasma cell disorder is achieved with chemotherapy, which is reflected by at least a 50% reduction in the difference between the concentration of the involved and uninvolved serum free light chain, survival is significantly increased. Serum levels of N-terminal pro-brain natriuretic peptide and troponin T, which are sensitive markers of myocardial dysfunction and predict survival in AL amyloidosis, should be routinely monitored.

Among patients with the nephrotic syndrome, a normal serum creatinine and no echocardiographic evidence of cardiac amyloidosis are associated with a higher response rate (39%) to chemotherapy, as defined by a 50% reduction in proteinuria without an increase in serum creatinine. Amyloid nephropathy requires supportive therapy of the nephrotic syndrome and of renal failure. Depending on the burden of their extrarenal disease, patients in endstage renal disease are candidates for regular dialysis and/or kidney transplantation. Their prognosis is compromised by the risks of extension of extrarenal deposition, especially to the heart, and by recurrence of amyloidosis in the graft if suppression of the plasma cell disorder has not been obtained with appropriate treatment.

Renal involvement in myeloma

Definition and epidemiology

Renal failure is one of the main complications of myeloma, found at presentation in 20% of patients and occurring in 50% during the course of the disease. It is mostly due to cast nephropathy, although other forms of renal disease may occur, including light-chain amyloidosis (10% of myeloma patients), light-chain deposition disease (5%), Fanconi’s syndrome, infiltration of renal interstitium by plasma cells, calcium precipitation, and renal infection. Myeloma cast nephropathy is due both to alterations in tubule cells induced by massive reabsorption of light chains in proximal tubule cells, and to cast formation involving light chains and Tamm–Horsfall protein in the distal tubule. The risk of developing renal failure is twice as high in patients with pure light-chain myeloma, and 5 to 6 times greater in patients with light-chain proteinuria of more than 2.0 g/day compared with those with proteinuria of less than 0.05 g/day.

Clinical presentation

Myeloma cast nephropathy usually presents as acute or subacute renal failure, often revealing myeloma with a high tumour burden (found in 70–80% of myeloma patients with renal failure). Common triggering factors include hypercalcaemia, dehydration, infection, use of toxic compounds including radiocontrast media, nonsteroidal anti-inflammatory drugs, diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, all of which reduce renal perfusion, especially in those who are dehydrated.

Renal failure induced by cast nephropathy is remarkably silent. The clinical and urinary syndrome is characterized by nonspecific signs including weakness, weight loss, bone pain, and signs of infection, all due to myeloma, and by urinary excretion of a monoclonal light chain. It must be emphasized that urinary dipsticks do not detect the light chain, which is measured by quantitative tests of proteinuria. Light chain accounts for more than 70% of total proteinuria by urine electrophoresis.

Tubular dysfunction is rarely a presenting symptom. Fanconi’s syndrome due to proximal tubule impairment may result from toxicity of intratubular inclusions of κ‎ light chains, usually organized into crystals. This can lead to osteomalacia and may precede the diagnosis of myeloma by several years.


Diagnosis of myeloma cast nephropathy relies on the detection of a urinary monoclonal light chain in patients with subacute or acute renal failure of apparently unknown origin. In those patients with pure light-chain myeloma, diagnosis can be suspected before urinalysis on the basis of dramatic hypogammaglobulinaemia detected by serum electrophoresis.

A renal biopsy should not be performed routinely in patients with a presumed diagnosis of myeloma cast nephropathy. It can, however, be useful for several reasons: first, to analyse tubulointerstitial lesions and allow diagnosis and treatment of other potential causes of renal impairment in those with multiple possible precipitating factors (infection, drugs, etc.); second, to establish the diagnosis of Fanconi’s syndrome; and third, to identify glomerular lesions in patients with albuminuria over 1 g/day and no evidence of amyloid deposits in ‘peripheral’ biopsies. Myeloma casts have unique characteristics, including a ‘fractured’ appearance due to crystal formation, polychromatism when stained with Masson’s trichrome, and the presence of multinucleated giant cells. They are consistently associated with dramatic epithelial tubular lesions and interstitial inflammatory infiltrates.


The first aim of treatment is to prevent or retard renal impairment in all patients with myeloma, most particularly those with light-chain myeloma, by prevention of dehydration, maintenance of a high urinary output and urine alkalinization, avoidance of nephrotoxic drugs, and control of hypercalcaemia (if present), which requires correction of salt and water deficit, steroids, and/or bisphosphonates, which are potent inhibitors of osteoclast activity but must be used with caution as they can be associated with acute renal failure.

Renal failure of recent onset should be promptly and vigorously managed. Intravascular depletion must be rapidly corrected by intravenous infusion of 0.9% saline, after which a high urinary output should be maintained whenever possible by continued saline and/or forced alkaline diuresis (which may help to prevent intratubular light-chain precipitation). Plasma exchange has been advocated to remove light chains more rapidly, but its value is unproven. In patients with oliguria, dialysis should be provided early. Recently, it has been shown that an extended haemodialysis protocol, using a new generation dialyser with very high permeability to proteins, was highly efficient in removing circulating free LC. In preliminary studies, this approach combined with chemotherapy, resulted in dialysis withdrawal in more than 60% of patients with myeloma cast nephropathy and severe renal failure.

Most patients with overt myeloma cast nephropathy should be promptly given chemotherapy to reduce the production of monoclonal light chains, which is justified because partial or complete recovery of renal function occurs in approximately one-half of patients. Only patients with refractory haematological disease should be given purely symptomatic treatment. However, median survival in those with progressive renal failure (about 2 years) remains shorter than that of patients without renal failure (3 to 4 years).

The optimum use of chemotherapy in patients with multiple myeloma and renal failure is uncertain. Conventional chemotherapies can induce remissions, but they have not markedly lengthened median survival. The low-dose oral melphalan–prednisone regimen has slow antitumour action, requires reduction of melphalan doses in patients with altered renal function, and melphalan interferes with any attempt at subsequent stem cell mobilization, hence this approach is reserved for older patients not eligible for more aggressive treatments. An intravenous regimen, such as VAD, induces earlier remission and is safer in those with renal failure because the drugs are metabolized in the liver, but the use of VAD has declined due to the neurotoxicity of vincristine. High-dose oral dexamethasone, which induces rapid decrease in serum free monoclonal light chains and has potent anti-inflammatory effects, can be introduced immediately after diagnosis and has the advantage of avoiding the use of a central line. It may be used alone or in combination with thalidomide, or with the proteasome inhibitor bortezomib, which appears to be well tolerated even in patients with severe renal failure. However, safety and efficiency of these protocols remain to be evaluated in controlled trials. Monitoring of serum free light chains should be performed to optimize therapy.

In younger patients (those aged less than 60) with multiple myeloma and persistent renal failure, high-dose melphalan followed by autologous stem cell transplantation should be considered because substantially longer survival and renal response can be achieved. However, to reduce toxicity and treatment-related mortality, high-dose regimen should consist of melphalan 140mg/m2. The indication for the procedure should be carefully evaluated if creatinine clearance is < 30ml/min, and restricted to patients with chemosensitive disease and good performance status.

In patients with irreversible renal failure and in those whose renal function deteriorates later, regular dialysis may be indicated if allowed by the patient’s general clinical condition. Recombinant human erythropoietin may be helpful to correct anaemia, although very high doses (and therefore great expense) are likely to be needed, and regular blood transfusion is often preferred.

Light-chain, light- and heavy-chain, and heavy-chain deposition disease

Definition and epidemiology

It has been known since the late 1950s that nonamyloidotic forms of glomerular disease resembling the lesion of diabetic glomerulosclerosis could occur in multiple myeloma. Randall and associates recognized the presence of monoclonal light chains in these lesions in 1976, defining light-chain deposition disease. Monoclonal heavy chains can also be found in association with light chains (defining light- and heavy-chain deposition disease), or occasionally in the absence of light chains (heavy-chain deposition disease). In clinical and pathological terms, light-chain deposition disease, light- and heavy-chain deposition disease, and heavy-chain deposition disease are similar and hence are also collectively referred to as (Randall-type) monoclonal Ig deposition disease (MIDD). They differ from amyloidosis by the lack of affinity for Congo red and fibrillar organization. MIDD occurs in a wide range of ages (31–79 years) with a slight male preponderance. Myeloma accounts for 45% of cases, but as in amyloidosis a monoclonal plasma cell proliferation can be found in virtually all patients by immunofluorescence examination of the bone marrow with specific anti-heavy and anti-light chain antisera.

Clinical presentation

Light-chain deposition disease is a systemic disease with deposition of Ig light chains along basement membranes in most tissues. However, deposition in tissues other than the kidney is often (but not always) totally asymptomatic and renal involvement dominates clinical presentation, mainly in the form of proteinuria and renal failure. In 23 to 67% of patients with light-chain deposition disease, albuminuria is associated with the nephrotic syndrome. In 25%, the urinary albumin output is less than 1 g/day, and these patients mainly exhibit a tubulointerstitial syndrome. Haematuria is more frequent (44%) than one would expect for a nephropathy in which cell proliferation is usually modest. Renal failure is remarkable for its high prevalence (89%), early appearance, and severity, irrespective of urinary albumin output. Hypertension occurs in approximately one-half of patients.


Diagnosis of MIDD relies on the association of the clinical features described above with the finding of a monoclonal Ig component in the serum and/or the urine. Since this component cannot be detected even by immunofixation in 15 to 30% of patients, the diagnosis of MIDD is mostly made by renal biopsy. In virtually all patients with this condition tubular lesions are characterized by the deposition of periodic acid–Schiff-positive ribbon-like material along the basement membrane. This is usually associated with a marked interstitial fibrosis and nodular glomerulosclerosis (found in two-thirds of patients with light-chain deposition disease and in all patients with heavy-chain deposition disease reported so far). Nodules are composed of membrane-like material with nuclei at the periphery (Fig. A key step in the diagnosis of the various forms of Randall-type MIDD is immunofluorescence examination of the biopsy specimen, revealing evidence of monotypic light- and/or heavy-chain deposits along glomerular and tubular basement membranes in all cases. By contrast with light-chain amyloidosis, the κ‎ isotype is 2 to 3 times more frequent than the λ‎ isotype, with a predominance of the Vκ‎4 subgroup. In those patients with heavy-chain deposition disease, a deletion of the first constant domain of the heavy chain can invariably be demonstrated by immunofluorescence analysis of the kidney specimen with specific antisera. Finally, nonfibrillar granular electron-dense deposits are visible by electron microscopy along tubular basement membranes and in glomerular lesions.

Fig. Monoclonal Ig deposition disease. (a) Typical nodular glomerulosclerosis. Note the membrane-like material in the centre of the nodules and nuclei at the periphery. Some glomerular capillaries show double contours. Note also thickening of the basement membrane of atrophic tubules. Masson’s trichrome stain, magnification ×312. (b) Bright staining of tubular basement membranes and mesangial nodules and, to a lesser extent, of glomerular basement membrane with anti-κ‎ antibody in a case of κ‎ light-chain deposition disease. Immunofluorescence, magnification ×312.

Monoclonal Ig deposition disease. (a) Typical nodular glomerulosclerosis. Note the membrane-like material in the centre of the nodules and nuclei at the periphery. Some glomerular capillaries show double contours. Note also thickening of the basement membrane of atrophic tubules. Masson’s trichrome stain, magnification ×312. (b) Bright staining of tubular basement membranes and mesangial nodules and, to a lesser extent, of glomerular basement membrane with anti-κ‎ antibody in a case of κ‎ light-chain deposition disease. Immunofluorescence, magnification ×312.


The natural history of MIDD is more uncertain than that of light-chain amyloidosis because extrarenal deposits can be totally asymptomatic or cause severe organ damage, including severe heart failure, pulmonary disease, and occasionally hepatic insufficiency or portal hypertension. The 5-year actuarial rates for patient survival and survival free of endstage renal failure (with chemotherapy) are 70% and 39%, respectively.

Patients with MIDD and myeloma should be treated with conventional chemotherapy if they are over 60 years of age, but intensive chemotherapy with autologous stem cell transplantation should be discussed in younger patients (see above). The correct treatment for those without myeloma is uncertain, the rarity of the disease meaning that there are no controlled trials. Deposited light chains have disappeared in isolated instances after intensive therapy. A pragmatic approach is to use alkylating agents plus prednisone or dexamethasone, or bortezomib-based regimens, in those with moderate but rapidly progressive renal insufficiency in an endeavour to prevent progression to endstage renal failure, but not to treat those with severe renal failure unless there are significant extrarenal complications. Serial monitoring of serum free light chain concentrations using nephelometric immunoassay is mandatory to assess haematological response to therapy. Recurrence of the disease has usually been observed in the few patients who have received renal transplants.

Non-Randall-type MIDD

Few cases of proliferative glomerulonephritis with monoclonal Ig deposits that do not display the characteristic features of Randall-type MIDD have been described. Almost all patients present initially with renal failure, proteinuria, and microscopic haematuria, with nephrotic syndrome and hypertension in more than 50% of patients. Non-Randall-type MIDD is a renal-limited disease. Whereas a serum and/or urine monoclonal component is detected in 60% of patients, only 10% have evidence of associated lymphoproliferative or plasma cell disorder. Activation of the classical or alternative complement pathway is present in 25% of cases. Endocapillary proliferative glomerulonephritis or membranoproliferative glomerulonephritis are the most common patterns of glomerular lesions. Electron-dense granular deposits of nondeleted IgG, IgA, or light chain are located in mesangial and paramesangial areas, and in subendothelial and/or subepithelial areas of glomerular basement membranes. These deposits do not usually show significant organization at the ultrastructural level. At variance with Randall-type MIDD, deposits are not found around tubular basement membranes or in vascular walls around myocytes.

Nonamyloid fibrillary and immunotactoid/microtubular glomerulopathies

Definition and epidemiology

Fibrillary glomerulonephritis and immunotactoid glomerulopathy are characterized (respectively) by fibrillar and microtubular deposits in the mesangium and the glomerular capillary loops. These deposits do not have a β‎-pleated sheet organization and are readily distinguishable from amyloid by the larger thickness of fibrils and the lack of Congo red staining. Whether they are totally distinct entities has been the subject of considerable debate. However, it is now established that the distinction between the two diseases is of great clinical and pathophysiological interest in the context of plasma cell dyscrasias, because monotypic deposits are detected in 50 to 80% of immunotactoid/microtubular glomerulopathies (sometimes referred to as GOMMID), while they are found in fewer than 20% of fibrillary glomerulopathies.

The prevalence of glomerulopathy with nonamyloid deposition of fibrillary or tubular material in a nontransplant adult biopsy population is around 1%, but this is almost certainly an underestimate because insufficient attention is given to atypical reactions with histochemical stains for amyloid and also most specimens are not examined by electron microscopy. The age range extends from 10 to 80 years with a peak incidence between 40 and 60 years.

Clinical presentation

The usual presentation is with the nephrotic syndrome, microscopic haematuria, and hypertension. Extrarenal manifestations, including skin and peripheral nerve involvement, have been described, almost exclusively in immunotactoid/microtubular glomerulopathy, which—at variance with fibrillary glomerulopathy—often occurs in the setting of chronic lymphocytic leukaemia or lymphoma.


Diagnosis relies entirely on analysis of the renal biopsy specimen by immunofluorescence microscopy with anti light chain and anti IgG subclass antibodies, and by electron microscopy. In immunotactoid/microtubular glomerulopathy this reveals either atypical membranous glomerulonephritis (often associated with segmental mesangial proliferation) or lobular membranoproliferative glomerulonephritis. Immunofluorescence shows coarse granular deposits of IgG and C3 along capillary basement membranes and in mesangial areas. Monotypic deposits composed of either IgG1, IgG2, or IgG3 (usually with a κ‎ light chain) are common. Using sensitive techniques such as immunoblotting, a circulating monoclonal Ig is detected in approximately 60% of patients. Electron microscopy shows immunotactoid/microtubular glomerulopathy to be remarkable for the presence of organized deposits of thick-walled microtubules with a central hollow core, 10 to 60 nm in diameter (usually greater than 30 nm), at times arranged in parallel arrays (Fig. When immunotactoid/microtubular glomerulopathy occurs in the setting of chronic lymphocytic leukaemia or related B-cell lymphoma, inclusions showing the same microtubular organization and containing the same IgG subclass and light-chain type as the renal deposits are often detected in the cytoplasm of leukaemic lymphocytes in the blood.

Fig. Immunotactoid/microtubular glomerulopathy in a patient with chronic lymphocytic leukaemia. Atypical membranous glomerulonephritis showing exclusive staining of the deposits with anti- γ‎ (a) and anti- κ‎ (b) antibodies. Immunohistochemistry, alkaline phosphatase, magnification × 312. (c) Electron micrograph of glomerular basement membrane, showing the microtubular structure of the subepithelial deposits. Uranyl acetate and lead citrate, magnification × 12 000.

Immunotactoid/microtubular glomerulopathy in a patient with chronic lymphocytic leukaemia. Atypical membranous glomerulonephritis showing exclusive staining of the deposits with anti- γ‎ (a) and anti- κ‎ (b) antibodies. Immunohistochemistry, alkaline phosphatase, magnification × 312. (c) Electron micrograph of glomerular basement membrane, showing the microtubular structure of the subepithelial deposits. Uranyl acetate and lead citrate, magnification × 12 000.

(From Béatrice Mougenot’s personal collection.)

Mesangial proliferation and membranoproliferative glomerulonephritis are the commonest lesions observed in nonamyloid fibrillary glomerulonephritis. Immunofluorescence studies show predominant polyclonal IgG4, usually associated with IgG1 deposits. Electron microscopy shows the fibrils, devoid of a central lumen, to be randomly arranged with a diameter varying between 12 and 22 nm. In almost all cases there is no evidence of associated lymphoproliferative disorder or monoclonal gammopathy.

Infection with hepatitis C virus has sometimes been reported in patients with nonamyloid fibrillary glomerulonephritis and immunotactoid glomerulopathy.


In patients with GOMMID, especially in those with chronic lymphocytic leukaemia, corticosteroids and/or chemotherapy are associated with partial or complete remission of the nephrotic syndrome, parallel with improvement of the haematological condition. More variable results are obtained with these treatments in patients with fibrillary glomerulonephritis. Recurrence of these diseases has been reported in patients receiving a renal allograft.

Renal involvement in cryoglobulinaemia

Definition and epidemiology

Cryoglobulinaemia is a pathological condition in which the blood contains Igs that precipitate on cooling (4°C) and resolubilize on warming (37°C). According to Brouet’s classification, there are three types of cryoglobulinaemia defined by their composition. Renal involvement is observed mainly in patients with mixed type II cryoglobulinaemia involving a monoclonal IgM (most often including a κ‎ light chain) with rheumatoid factor activity and a polyclonal IgG. Type II cryoglobulinaemia can be associated with overt lymphoproliferative disorders of the B-cell lineage, although in many cases no underlying haematological disorder is found such that this type of cryoglobulinaemia has long been referred to as essential mixed cryoglobulinaemia. Glomerular disease may also occur in type I cryoglobulinaemia, composed of a single monoclonal Ig (mostly IgM or IgG), usually in the context of underlying lymphoproliferative or plasma cell disorder (see later).

Viral infections may trigger the formation of cryoglobulin. Whereas hepatitis B and Epstein–Barr virus infections have been implicated in the past, the role of hepatitis C virus infection is now recognized to be an important factor in the pathogenesis of type II cryoglobulinaemia. Antibodies to hepatitis C virus and hepatitis C virus RNA are found in the sera of most patients with type II cryoglobulinaemia, probably explaining the uneven geographical distribution of mixed cryoglobulinaemias, which predominate in southern Europe where hepatitis C infection is more prevalent.

The condition is commonest in adults in the fifth and the sixth decades of life, with a slight female predominance.

Clinical presentation

Renal disease most often occurs in patients with a long history of cryoglobulinaemia-related vasculitic symptoms, including palpable purpura (70%), arthralgias (50%), fatigue, Raynaud’s phenomenon, peripheral neuropathy (22%), and hepatic involvement.

The renal disease may present as an acute nephritic syndrome (in 20 to 30% of patients) with gross haematuria, heavy proteinuria, hypertension, and renal failure of sudden onset, sometimes with oliguria (5% of patients). The pathological finding in these patients is membranoproliferative glomerulonephritis with the presence of numerous intraluminal thrombi and/or necrotic vasculitic lesions. Remission may occur spontaneously or during therapy, with relapses following in up to 20% of cases.

Most patients with mixed cryoglobulinaemia (55%) have an indolent and protracted renal course, presenting with proteinuria, haematuria, and hypertension. The usual renal lesion in this context is membranoproliferative glomerulonephritis, with some of the peculiarities described above.

Nephrotic syndrome affects another 20% of patients. Arterial hypertension is observed in more than 80% of patients at the time of onset of renal disease. Endstage renal disease develops in fewer than 10% of patients. It should be stressed that the overall risk of non-Hodgkin B-cell lymphomas is 35 times higher in patients with hepatitis C virus-related cryoglobulinaemia compared to the general population.


Mixed type II cryoglobulinaemia should be suspected in patients with the clinical picture described above, an IgM rheumatoid factor, and a very low serum C4 fraction and total haemolytic activity of complement. In this context a careful search for the presence of cryoglobulin must be made, requiring that a blood sample from a fasting patient should be placed in warm water and taken promptly to the laboratory, which needs to be forewarned that such a sample will arrive.

Cryoglobulinaemia-related membranoproliferative glomerulonephritis usually shows several distinctive histological features, including massive subendothelial deposits filling the capillary lumen and forming so-called thrombi, and dramatic infiltration by leucocytes, mainly monocytes (Fig. The thrombi are brightly stained with anti-μ‎ and anti-κ‎ antibodies and present a microtubular crystalline structure similar to that of the cryoprecipitate. These glomerular changes may be associated with acute vasculitis of the small and medium-sized arteries (33%) and lymphocytic infiltrates in the interstitium. Crescentic extracapillary proliferation is rare and always limited.

Fig. Cryoglobulinaemic glomerulonephritis. (a) The glomerulus shows a marked endocapillary hypercellularity with massive infiltration of mononuclear leucocytes. Masson’s trichrome stain, magnification × 500. (b) Frequent doublecontour aspect and intraluminal thrombi. Periodic acid–Schiff stain, magnification × 312. (c) Thrombi and segments of glomerular basement membrane are brightly stained with anti-IgM antibody. Immunofluorescence, magnification × 312.

Cryoglobulinaemic glomerulonephritis. (a) The glomerulus shows a marked endocapillary hypercellularity with massive infiltration of mononuclear leucocytes. Masson’s trichrome stain, magnification × 500. (b) Frequent doublecontour aspect and intraluminal thrombi. Periodic acid–Schiff stain, magnification × 312. (c) Thrombi and segments of glomerular basement membrane are brightly stained with anti-IgM antibody. Immunofluorescence, magnification × 312.

(From Béatrice Mougenot’s personal collection.)


The best treatment of mixed cryoglobulinaemia is not firmly established because the course of the disease is unpredictable and acute exacerbations may remit spontaneously. In patients with moderate renal and extrarenal manifestations, immunosuppressive agents are not indicated. In those with hepatitis C virus infection, combined pegylated interferon and ribavirin for at least 1 year appears to be the treatment of choice, the dose of the latter being adapted according to renal function to prevent haemolytic anaemia, which may require supplementary recombinant erythropoietin therapy. In more severe cases, particularly those with signs of systemic vasculitis, high-dose steroids, plasma exchange, and cyclophosphamide or monoclonal anti-CD20 antibody (rituximab) are indicated. Rituximab, which is usually well tolerated, appears to be as efficient as cyclophosphamide. Because ribavirin and pegylated interferon are not recommended in patients with advanced renal failure, standard interferon should be used for controlling virus replication enhanced by steroids and/or immunosuppressive agents. Hypertension needs to be carefully controlled because cardiovascular complications are the major causes of death.

Renal involvement in Waldenström’s macroglobulinaemia

A glomerulonephritis with intracapillary thrombi of monoclonal IgM is rare, but is almost specific for Waldenström’s macroglobulinaemia. It is characterized by periodic acid-Schiff-positive, noncongophilic endomembranous deposits in a variable number of capillary loops, which are sometimes so large as to occlude the capillary lumen either partially or completely, thus forming thrombi. There may also be a B-cell interstitial infiltrate. Renal presentation is with proteinuria or renal impairment. Some patients have a cryoglobulin, in others the amount of circulating IgM seems to be higher than that in patients with Waldenström’s macroglobulinaemia without obvious renal involvement, or with amyloidosis, leading to the suggestion that hyperviscosity is important in the pathogenesis of the renal lesion. The haematological condition is treated on its own merits (see Chapter 22.4.5). In those with acute renal failure there is anecdotal experience that plasma exchange can be effective in restoring renal function at least temporarily, allowing time for other treatments to be applied.

Renal involvement in lymphomas and leukaemias

Renal complications of lymphomas and leukaemias are summarized in Box All patients with unexplained renal failure should undergo ultrasound examination of the kidney, which should be arranged as a matter of urgency, to identify either enlarged kidneys due to tumour infiltration or hydronephrosis. The presence of heavy albuminuria in this setting is suggestive of paraneoplastic glomerulopathy.

Hodgkin’s disease and non-Hodgkin’s lymphoma

Glomerulonephritis is a rare complication of lymphoma, most often described in patients with Hodgkin’s disease, of whom 0.4% have minimal-change disease and 0.1% have AA amyloidosis. This low incidence of amyloidosis in patients with Hodgkin’s disease is most likely attributable to modern treatment protocols that induce rapid remission. Hodgkin’s lymphoma-related minimal-change disease shows features of a paraneoplastic glomerulopathy. The nephrotic syndrome usually appears early, revealing the haemopathy in about one-half of the cases; it rapidly disappears after effective treatment of the underlying condition; and it usually relapses simultaneously with the haemopathy. Cases of crescentic glomerulonephritis with rapidly progressive renal failure due to antiglomerular basement antibodies have also been reported.

Glomerulonephritis may also occur in patients with non-Hodgkin’s lymphoma, including both T- and B-cell proliferations. In these conditions, unlike in Hodgkin’s lymphoma, minimal-change disease is uncommon, and membranoproliferative glomerulonephritis and necrotizing crescentic glomerulonephritis with or without vasculitis are the most frequent lesions. Some cases are associated with type I cryoglobulinaemia or GOMMID. In other cases the association between non-Hodgkin’s lymphoma and renal disease may be coincidental. Presenting renal symptoms are nephrotic syndrome and/or renal impairment. Full remission of these symptoms can be achieved in some patients by aggressive therapy of the lymphoma.

Chronic lymphocytic leukaemia and low-grade B-cell lymphoma

These haemopathies, particularly chronic lymphocytic leukaemia, have been reported in association with glomerular disease in about 50 cases. Most commonly the nephropathy, usually manifesting as nephrotic syndrome with impaired renal function, and the leukaemia are detected simultaneously. The most frequent glomerular disease is membranoproliferative glomerulonephritis with or without cryoglobulinaemia (mostly type I). In type I cryoglobulinaemic glomerulonephritis, glomerular monoclonal Ig deposits often display an ultrastructural organization into microtubules, and less frequently into crystals. In the absence of cryoglobulinaemia, a molecular link can be established between the haemopathy and the glomerulopathy when monotypic Ig deposits are found in the glomerulus, which can occur even in the absence of detectable circulating M component. As discussed previously, some of these patients present with typical immunotactoid/microtubular glomerulopathy or MIDD. Improvement of the nephropathy after treatment for the leukaemia is well described.

Acute leukaemias

Disseminated intravascular coagulation has been associated with acute progranulocytic leukaemia. Other renal complications are commonly due to treatment, most particularly the tumour lysis syndrome (see below).

POEMS syndrome

POEMS syndrome is a rare condition defined by the presence of peripheral neuropathy, organomegaly, endocrinopathy (excluding diabetes mellitus or hypothyroidism), monoclonal plasma cell disorder (IgA, IgG, or IgM, almost always associated with a λ‎ light chain), and skin changes. The association of POEMS syndrome with osteosclerotic myeloma or Castleman’s disease is common. Although the pathophysiology of the disease is unknown, POEMS syndrome is characterized by increased production of proinflammatory cytokines (interleukin-1 and 6, tumour necrosis factor-α‎) and vascular endothelial growth factor. Renal disease may occur, which usually manifests as proteinuria, haematuria, and renal failure that may progress to endstage renal failure. Kidney biopsy reveals lesions resembling thrombotic microangiopathy, with glomerular enlargement, cellular proliferation, and mesangiolysis with marked swelling of endothelial and mesangial cells, associated with endarteritis-like lesions in the small renal arteries. The monoclonal component is usually not deposited in kidney.

Tumour lysis syndrome

Tumour lysis syndrome is a life-threatening metabolic emergency. It occurs in patients with haemopathies involving a high cell turnover, such as Burkitt’s lymphoma or acute leukaemia, mostly at the onset of chemotherapy and/or on radiation therapy. The ensuing massive cytolysis generates high levels of uric acid, phosphate, potassium, and xanthine (especially in patients treated with allopurinol), with a concomitant decrease in serum calcium concentration. Oliguric or anuric acute renal failure may occur, especially in those who are dehydrated or have pre-existing impairment of kidney function. This acute renal failure is mostly the consequence of acute precipitation of urate crystals in the tubular lumen, but in those with a moderate increase in uric acid concentration the role of severe hyperphosphataemia causing precipitation of calcium/phosphate complexes in renal interstitium and the tubular system has been assumed.

Prevention is better than cure, and intensive monitoring is mandatory to prevent the development and the consequences of this syndrome. Patients at risk of the tumour lysis syndrome should be vigorously hydrated with 0.9% saline (assuming normal or near normal baseline renal function, and with care taken to avoid inducing pulmonary oedema) before receiving chemotherapy or radiotherapy. Urinary alkalinization should be used with caution because it may induce phosphate precipitation. Reduction of urate production with allopurinol, which increases the risk of formation of xanthine nephropathy/stones due to accumulation of xanthine, should be reserved for patients at low risk for developing tumour lysis syndrome. In high-risk patients (high tumour burden, aggressive chemotherapy, hypovolaemia) with hyperuricaemia, recombinant modified urate oxidase (rasburicase) should be preferred, which rapidly reduces the uric acid pool, prevents accumulation of xanthine and hypoxanthine, and does not require alkalinization for effect. Rasburicase is also indicated in the treatment of established tumour lysis syndrome, associated with vigorous hydration with 0.9% saline to encourage urinary output in patients passing urine, with close clinical monitoring to prevent iatrogenic fluid overload. Patients with severe acute renal failure should be treated with haemodialysis, which allows recovery of renal function following the reduction of serum phosphate and serum uric acid concentrations.

Further reading

Touchard G (2003). Ultrastructural pattern and classification of renal monoclonal immunoglobulin deposits. In: Touchard G, et al. (eds) Monoclonal gammopathies and the kidney, pp. 95–117. Kluwer, Dordrecht.Find this resource:

    Renal involvement in Ig light-chain amyloidosis

    Comenzo RL, Gertz MA (2002). Autologous stem cell transplantation for primary systemic amyloidosis. Blood, 99, 4276–82.Find this resource:

    Dispenzieri A, et al. (2004). Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol, 22, 3751–7.Find this resource:

    Guidelines Working group of UK Myeloma Forum; British Committee for Standards in Haematology; British Society for Haematology (2004). Guidelines on the diagnosis and management of AL amyloidosis. Br J Haematol, 125, 681–700.Find this resource:

    Jaccard A, et al. (2007). High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med, 357, 1083–93.Find this resource:

    Kastritis E, et al. (2010). Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol, 28, 1031–7.Find this resource:

    Kyle RA, Gertz MA (1995). Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol, 32, 45–59.Find this resource:

    Floege J, Johnson RJ, Feehally J (eds) (2010). Renal amyloidosis and glomerular diseases with monoclonal immunoglobulin deposition. Comprehensive clinical nephrology, 4th edition, pp.322–34. Saunders Elsevier, London.Find this resource:

      Skinner M, et al. (2004). High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med, 140, 85–93.Find this resource:

      Vrana JA, et al. (2009). Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood, 114, 4957–9.Find this resource:

      Renal involvement in myeloma

      Chanan-Khan AA, et al. (2007). Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood, 109, 2604–6.Find this resource:

      Dimopoulos MA, et al. (2010). Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol, 28, 4976–84.Find this resource:

      Hutchison CA, et al. (2007). Efficient removal of immunoglobulin free light chains by hemodialysis for multiple myeloma: in vitro and in vivo studies. J Am Soc Nephrol, 18, 886–95.Find this resource:

      Korbet SM, Schwartz MM (2006). Multiple myeloma. J Am Soc Nephrol, 17, 2533–45.Find this resource:

      Ronco PM, Aucouturier P, Mougenot B (2005). Kidney involvement in plasma cell dyscrasias. In: Davison, Cameron, Grünfeld, Kerr et Ritz, Winearls (eds) Oxford textbook of Clinical Nephrology, 3rd edition, vol 2, pp. 709–32. Oxford University Press, Oxford.Find this resource:

        Light-chain, light and heavy-chain, heavy-chain deposition disease

        Heilman RL, et al. (1992). Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. Am J Kidney Dis, 20, 34–41.Find this resource:

        Lin J, et al. (2001). Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol, 12, 1482–92.Find this resource:

        Moulin B, et al. (1999). Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy chains lacking CH1. J Am Soc Nephrol, 10, 519–28.Find this resource:

        Pozzi C, et al. (2003). Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis, 42, 1154–63.Find this resource:

        Ronco PM, Aucouturier P, Moulin B (2010). Renal amyloidosis and glomerular diseases with monoclonal immunoglobulin deposition. In: Floege J, Johnson RJ, Feehally J (eds) Comprehensive clinical nephrology, 4th edition, pp. 322–34. Saunders Elsevier, London.Find this resource:

          Royer B, et al. (2004). High dose chemotherapy in light chain or light and heavy chain deposition disease. Kidney Int, 65, 642–48.Find this resource:

          Non-Randall-type MIDD

          Nasr SH, et al. (2004). Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity mimicking immune-complex glomerulonephritis. Kidney Int, 65, 85–96.Find this resource:

          Touchard G (2003). Ultrastructural pattern and classification of renal monoclonal immunoglobulin deposits. In: Touchard G, et al. (eds) Monoclonal gammopathies and the kidney, pp. 95–117. Kluwer, Dordrecht.Find this resource:

            Nonamyloid fibrillary and immunotactoid glomerulopathies

            Brady HR (1998). Fibrillary glomerulopathy. Kidney Int, 53, 1421–29.Find this resource:

            Bridoux F, et al. (2002). Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathy are associated with distinct immunologic features. Kidney Int, 62, 1764–75.Find this resource:

            Fogo A, Qureshi N, Horn RG (1993). Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy. Am J Kidney Dis, 22, 367–77.Find this resource:

            Rosenstock JL, et al. (2003). Fibrillary and immunotactoid glomerulonephritis: distinct entities with different clinical and pathologic features. Kidney Int, 63, 1450–61.Find this resource:

            Touchard G, et al. (1994). Glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits. Adv Nephrol Necker Hosp, 23, 149–75.Find this resource:

            Renal involvement in cryoglobulinaemia

            Brouet JC, et al. (1974). Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med, 57, 775–88.Find this resource:

            D’Amico G (1998). Renal involvement in hepatitis C infection: cryoglobulinemic glomerulonephritis. Kidney Int, 54, 650–71.Find this resource:

            Matignon M, et al. (2009). Clinical and morphologic spectrum of renal involvement in patients with mixed cryoglobulinemia without evidence of hepatitis C virus infection. Medicine (Baltimore), 88, 341–48.Find this resource:

            Saadoun D, et al. (2006). Antiviral therapy for hepatitis C virus-associated mixed cryoglobulinemia vasculitis. Arthritis Rheum, 54, 3696–706.Find this resource:

            Sansonno D, et al. (2003). Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alfa with an anti-CD20. Blood, 101, 3818–26.Find this resource:

            Renal involvement in Waldenström’s macroglobulinaemia

            Audard V, et al. (2008). Renal lesions associated with IgM-secreting monoclonal proliferations: revisiting the disease spectrum. Clin J Am Soc Nephrol, 3, 1339–49.Find this resource:

            Harada Y, et al. (2000). Nephrotic syndrome caused by protein thrombi in glomerulocapillary lumen in Waldenström’s macroglobulinaemia. Br J Haematol, 110, 880–83.Find this resource:

            Veltman GA, et al. (1997). Renal disease in Waldenström’s macroglobulinaemia. Nephrol Dial Transplant, 12, 1256–59.Find this resource:

            Renal involvement in lymphomas and leukaemias

            Moulin B, et al. (1992). Glomerulonephritis in chronic lymphocytic leukemia and related B-cell lymphomas. Kidney Int, 42, 127–35.Find this resource:

            Ronco PM (1999). Paraneoplastic glomerulopathies: new insights into an old entity. Kidney Int, 56, 355–77.Find this resource:

            Renal involvement in POEMS syndrome

            Nakamoto Y, et al. (1999). A spectrum of clinicopathological features of nephropathy associated with POEMS syndrome. Nephrol Dial Transplant, 14, 2370–8.Find this resource:

            Tumour lysis syndrome

            Cairo MS, Bishop M (2004). Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol, 127, 3–11.Find this resource:

            Haas M, et al. (1999). The spectrum of acute renal failure in tumour lysis syndrome. Nephrol Dial Transplant, 14, 776–9.Find this resource:

            Rampello E, et al. (2006). The management of tumor lysis syndrome. Nat Clin Pract Oncol, 3, 438–47.Find this resource: