Renal involvement in patients with rheumatoid arthritis

In rheumatoid arthritis (RA) kidney is commonly affected organ with clinical presentation characterised by proteinuria (often nephrotic range) and microhematuria followed by chronic renal failure. This condition is well recognized as a rheumatoid nephropathy (rheumatoid glomerulonephritis), which is mediated by an immunological inflammation and by nephrotoxic effects of numerous drugs usually used in rheumatoid arthiritis treatment, such as NSAID, DMARD. In the patohistological examination various kinds of associated renal lesions could be seen. The most often are amyloidosis, glomerulonephritis, interstitial nephritis. In this study, we presented 15 patients, 10 women and 5 men, mean age of 60.2 with average rheumatoid arthritis duration of 19.4 years and signs of rheumatoid nephropathy. In all patients renal biopsy was performed with frequency of histopathological findings as follows: amyloidosis in 5 patients, IgA nephropathy in 3 patients, FSGS in 3 patients, mesangial proliferative glomerulonephritis in 3 patients, minimal change disease, pauci-immune glomerulonephritis and thin membrane disease in 1 patient. In all patients (except patient with thin membrane nephropathy) we started immunossuppresive therapy with glucocorticoids in combination with cyclophosphamide or cyclosporin or azatioprine. In conclusion, in all patients with rheumatoid arthritis, parameters of renal function should be monitored and in the case of patologic results, renal biopsy should be be performed. In the treatment of RA patients with related renal disorder, suspected causal drug should be removed from the treatment and specific immunosuppressive therapy initiated.     

Hypocomplementemic urticarial vasculitis: report of a pediatric case

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is well described in adults but is quite rare in children. We report a pediatric case of HUVS initially diagnosed as juvenile rheumatoid arthritis and then as Henoch-Schönlein purpura. Beginning at 3 years of age, our patient developed polyarthritis with hypocomplementemia. She subsequently experienced an intermittent purpuric rash beginning at age 4 years, and she continued to have episodic arthritis and rash for years. Hematuria and proteinuria were noted at 12 years of age; renal biopsy revealed membranoproliferative glomerulonephritis with membranous features. Serum complement evaluation revealed activation of the classical pathway, consistent with HUVS. Therapy with oral dapsone led to improvement in proteinuria. HUVS should be considered in the differential diagnosis of pediatric patients with glomerulonephritis, urticarial rash, arthritis/arthralgias, and obstructive pulmonary disease.     

Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis associated with rheumatoid arthritis: An unusual case report

Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.     

IgG, IgA and IgM rheumatoid factors in patients with glomerulonephritis

Rheumatoid factors (RF), autoantibodies to IgG, have been postulated to have some pathogenetic role in the development of some types of glomerulonephritis. A simple and sensitive solid-phase fluorescence immunoassay was employed to determine whether IgG, IgA and IgM RF were detectable in sera from patients with various types of glomerulonephritis, rheumatoid arthritis (RA) and those with various streptococcal infections. IgG, IgA and IgM RF were significantly increased in the majority of patients with RA, lupus nephritis (SLE), acute poststreptococcal glomerulonephritis (APSGN) and various streptococcal infections. The titers of IgG and IgA RF were significantly higher in patients with APSGN than in those with simple pharyngitis. IgM RF was increated in patients with IgA nephropathy (IgA-N) and in those with membranoproliferative glomerulonephritis type I (MPGN). No significantly high RF was observed in membranous nephropathy (MN) or chronic mesangial proliferative glomerulonephritis without IgA deposition (PGN). It is suggested that some autologous immune mechanisms may be involved in the pathogenesis of some types of glomerulonephritis.     

Is there a role for TNF-alpha in anti-neutrophil cytoplasmic antibody-associated vasculitis? Lessons from other chronic inflammatory diseases

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis and immune-mediated pulmonary renal syndrome. Now that the acute manifestations of the disease generally can be controlled with immunosuppressive drugs, ANCA-associated vasculitis has become a chronic and relapsing inflammatory disorder. The need to develop safer and more effective treatment has led to great interest in the mediators of chronic inflammation. There are many lessons to be learned from studies of other chronic inflammatory diseases, particularly rheumatoid arthritis (RA). The identification of a TNF-alpha-dependent cytokine cascade in the in vitro cultures of synovium in joints of patients with RA led to studies of TNF blockade in experimental models of arthritis and subsequently to clinical trials. These have culminated in the widespread introduction of anti-TNF therapy not only in RA but also in Crohn disease, ankylosing spondylitis, and several other chronic inflammatory disorders. Following a similar investigative pathway, studies that show the importance of TNF production by leukocytes and intrinsic renal cells in glomerulonephritis have been followed by the demonstration of the effectiveness of TNF blockade in several experimental models of glomerulonephritis and vasculitis. In experimental autoimmune vasculitis, improvement in disease was paralleled by a reduction in leukocyte transmigration, as demonstrated by intravital microscopy. The benefit of infliximab (a mAb to TNF) in ANCA-associated vasculitis was recently reported in a prospective open-label study. However, the use of etanercept (a soluble TNF receptor fusion protein) was not found to be of significant benefit in a randomized, controlled trial in patients with Wegener granulomatosis. Therefore, there is a need for further evaluation of the use of anti-TNF antibodies in patients with ANCA-associated glomerulonephritis.     

Nephrotic syndrome revealing a disseminated Langerhans' cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a clonal disorder of proliferating histiocytes, which can affect various organs. The clinical picture ranges from localized to disseminated disease with multiple organ involvement and severe organ dysfunction. Renal involvement is uncommon and the association with glomerulonephritis is unusual. We report here a case of nephrotic syndrome caused by membranoproliferative glomerulonephritis (MPGN) in a 20-year-old woman, which revealed a disseminated form of LCH. Surgical removal of the LCH process and high doses of corticosteroids led to the remission of the basic disease and the renal involvement. The occurence of membranoproliferative glomerulonephritis in the course of LCH might be mediated by circulating immune complexes, composed at least in part of antigens or neoantigenes which may cause the abnormal proliferation of the Langerhans' cells.     

MPO-ANCA necrotizing glomerulonephritis related to rheumatoid arthritis

Two patients with rheumatoid arthritis (RA) developed necrotizing crescentic glomerulonephritis with high titers of anti-myeloperoxidase antibodies (MPO) in the absence of overt extrarenal vasculitis. We therefore suggest that in some patients with RA, MPO-ANCA necrotizing glomerulonephritis (GN) may occur as a kidney-limited form of rheumatoid vasculitis, and that RA should be added to the list of diseases potentially associated with necrotizing GN with anti-MPO antibodies. These observations also point out the importance of repeatedly evaluating titers of anti-MPO antibodies in the course of RA, especially if renal impairment or abnormal urinary sediment are present. (Am J Kidney Dis 1998 Nov;32(5):E6)     

Long-term follow-up of membranoproliferative glomerulonephritis type II and pregnancy: a case report

A 24-year-old female was diagnosed as having membranoproliferative glomerulonephritis type II (or dense deposit disease), 11 years prior to becoming pregnant. The patient's first renal biopsy was performed 5 years after the onset of her renal symptoms. This biopsy was compared to a second renal biopsy taken just before the patient became pregnant. The second renal biopsy only showed a slight progression in the disease process. During the course of pregnancy, neither renal insufficiency nor hypertension were clinically evident. However, both an increase in proteinuria and a transient hypoalbuminemia were observed. The pregnancy, labor and delivery, and postpartum course for both the mother and child were without complications. Cases of membranoproliferative glomerulonephritis type I and pregnancy have been reported. However, to our knowledge, there are few reports documenting the outcome of pregnancy when a patient has membranoproliferative glomerulonephritis type II. We suggest that it is possible for a patient with membranoproliferative glomerulonephritis type II to have an uneventful pregnancy if she has neither hypertension nor renal insufficiency.     

Atteinte rénale des cryoglobulinémies

Cryoglobulins are immunoglobulins that undergo reversible precipitation at low temperatures. They can induce systemic vasculitis, characterized by purpuric cutaneous lesions, arthritis, peripheral neuropathy, hypocomplementemia and glomerular disease. Renal pathology reveals membranoproliferative glomerulonephritis, with particularly intense mesangial cell proliferation and infiltration by macrophages, associated with intracapillary thrombi. This renal disease presents as a nephritic syndrome, with heavy proteinuria, haematuria severe hypertension and rapidly progressive kidney failure that can lead to end-stage renal disease. Hepatitis C is the main cause of mixed (type 2 or 3) cryoglobulinemia and requires the initiation of a specific antiviral therapy, together with immunosuppressive drugs. Rituximab is now considered as the best immunosuppressive therapy in this situation, inducing B-cell depletion, clearance of circulating cryoglobulin and resolution of renal symptoms. Monoclonal (type 1) cryoglobulinemia, is a rare condition, but it usually reveals an B-cell or a plasma cell proliferation, that require a specific hematological treatment to obtain remission of the renal disease.     

Necrotising, proliferative glomerulonephritis due to monoclonal cryoglobulinaemia

Renal involvement is uncommon in the rare condition of Type I cryoglobulinaemia. On review of the literature most cases featured membranoproliferative glomerulonephritis on renal biopsy. In this case report, we describe a presentation of rapidly progressive glomerulonephritis that histologically demonstrated necrotising, proliferative glomerulonephritis. Treatment with a cytotoxic agent and corticosteroids has resulted in clinical stability.     

Extracapillary glomerulonephritis with necrotizing vasculitis in D-penicillamine-treated rheumatoid arthritis

Rapidly progressive glomerulonephritis occurred in a woman with rheumatoid arthritis (RA) who had been treated with D-penicillamine for 3 months. Light microscopy study of the kidney showed severe glomerulonephritis with crescent formation in 50% of glomeruli and necrotizing vasculitis. Immunoflurescence revealed IgA and C3 granular deposits diffusely distributed along the capillary walls. The patient was treated with steroid 'pulse', antiplatelet agents and heparin and a partial recovery of renal function was observed after 2 months of anuria. This renal picture is unlike that reported in RA and a causative role for D-penicillamine is suggested.     

Resolution of hepatitis B virus-related membranoproliferative glomerulonephritis after orthotopic liver transplantation

The most well-described renal disease associated with hepatitis B virus (HBV) infection is membranous glomerulonephritis; membranoproliferative glomerulonephritis is described much less frequently. The course of HBV-associated renal disease after liver transplantation has not been described to date. We present a 15-year-old girl with HBV-associated membranoproliferative glomerulonephritis and end-stage liver disease, in whom, after cadaver liver transplantation, clinical and histological resolution of renal disease was observed. Resolution was associated with diminution of circulating HBV surface antigen levels.     

Crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis

We describe the association of crescentic membranoproliferative glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome. A 39-year-old woman presented edema and proteinuria and later a non-pruritic urticarial rash. Laboratory results showed nephrotic syndrome, hypocomplementemia and positive anti-C1q antibodies. Skin biopsy disclosed leukocytoclastic vasculitis. Acute renal failure developed. Renal biopsy revealed crescentic membranoproliferative glomerulonephritis. She was treated with corticosteroids and cyclosphosphamide with improvement of the renal function and partial remission of the nephrotic syndrome. Afterwards the nephrotic syndrome relapsed, mycophenolate mofetil in monotherapy was administered with reduction in proteinuria. As far as we know only 3 cases, 2 in children and one in an adult, of crescentic glomerulonephritis and hypocomplementemic urticarial vasculitis syndrome have been reported. In our patient renal manifestations preceded urticarial lesions. We provide information on the evolution during a 42-month follow-up.     

Necrotizing glomerulonephritis in rheumatoid arthritis

Rheumatoid arthritis may be associated with several glomerular lesions including amyloidosis, mesangial proliferation and membranous glomerulonephritis. Systemic vasculitis is a well-recognized extra-articular complication of rheumatoid arthritis, but necrotizing glomerulonephritis, the glomerular expression of vasculitis, has been described infrequently. This report comprises four patients with rheumatoid arthritis who underwent renal biopsy for declining renal function, proteinuria and active urine sediments. Pathology revealed that three patients had segmental necrotizing glomerulonephritis without significant glomerular immunoglobulin deposition. The fourth had segmental necrosis associated with diffuse membranous glomerulonephritis. We conclude that necrotizing glomerulonephritis is part of the spectrum of glomerular lesions seen in patients with rheumatoid arthritis. Because of therapeutic considerations involving the use of cyclophosphamide, necrotizing glomerulonephritis should be a diagnostic consideration in the rheumatoid arthritis patient with signs of glomerulonephritis and rapidly deteriorating renal function.     

Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity

Lobular glomerulonephritis is an entity first thought to have represented a primary disease of uncertain histogenesis, but more recently has generally been considered to represent a morphologic variant of membranoproliferative glomerulonephritis. We have encountered five patients who were found to have a lobular glomerulonephritis by renal biopsy, but in whom features of membranoproliferative glomerulonephritis types I, II, or III, could not be demonstrated and in whom alternate known diagnostic categories could be excluded. We suggest that lobular glomerulonephritis, or alternately, idiopathic nodular mesangial sclerosis, is an uncommon but persistent disease entity with a distinctive pathologic appearance and unknown pathogenesis.     

Pauci-immune necrotizing glomerulonephritis complicating rheumatoid arthritis

Necrotizing glomerulonephritis associated with rheumatoid arthritis typically occurs in the setting of frankly apparent systemic vasculitic signs and symptoms. We report two recent cases that differed from this paradigm. Both patients had rheumatoid arthritis and deteriorating renal function due to P-ANCA positive pauci-immune necrotizing crescentic glomerulonephritis, but minimal systemic symptoms. Delay in diagnosis and institution of appropriate therapy may have contributed to the dialysis dependence of one of these patients. We suggest that heightened suspicion of an aggressive necrotizing glomerulonephritis should be maintained in all patients with rheumatoid arthritis who present with acute renal insufficiency even in the absence of frank vasculitis.     

Hepatitis C and glomerulonephritis

Summary: Several systemic viral infections have been associated with the development of glomerular lesions. of the viruses that cause liver disease hepatitis B was the first to be recognized. the recent availability of serologic tests for the hepatitis C virus (HCV) has uncovered an association between HCV infection and renal disease. the principal glomerular lesion that develops is that of a membranoproliferative glomerulonephritis (MPGN), usually in association with antigenaemia and circulating immune complexes that have the characteristics of mixed cryoglobulinaemia represented by polyclonal IgG and monoclonal IgM with rheumatoid factor activity. the presence of a very high percentage of anti-HCV seropositivity in cryoglobulinaemic forms of MPGN suggests that the virus plays an important role in the pathogenesis of the associated immune complex glomerulonephritis. Precipitates containing HCV-RNA and circulating anti-HCV IgG and IgM have been found in the majority of such cases. the course of the renal disease that develops is progressive. Treatment with interferon alpha appears to attenuate the progression of the renal lesions, and the response to treatment appears to be closely related to the clearance of hepatitis C viraemia. Renal lesions also occur in the absence of clinical evidence of liver disease or mixed cryoglobulinaemia. In addition to MPGN, membranous glomerulonephropathy, IgA nephropathy and focal segmental glomerulosclerosis have been reported in these cases of HCV infection. the prevalence of glomerular lesions in patients with HCV infection remains to be determined. the available serologic tests for HCV are still in evolution. In the meantime, all patients presenting with glomerular disease should be screened for HCV.     

Steroid-responsive nephrotic syndrome in a child with juvenile idiopathic arthritis

Renal disease is rare in children with juvenile idiopathic arthritis, although a number of associated nephropathies have been described, including mesangial glomerulonephritis. We report the presence of mesangial glomerulonephritis, revealed by a nephrotic syndrome, in a paediatric patient with juvenile idiopathic arthritis. Short-term steroid treatment induced a rapid remission of the nephrotic syndrome, but the presence of anti-nuclear antibodies, 1:320 in a homogeneous pattern, irregular deposits of C1q in a renal biopsy, and a mother with episodes of cutaneous lupus suggested an uncertain renal evolution for this infant.     

Sibling cases of nephritis resembling membranoproliferative glomerulonephritis

We have experienced rare cases of membranoproliferative glomerulonephritis (MPGN)-like nephritis, which was seen in siblings. Both the brothers had asymptomatic hematuria and proteinuria at an age before 10, 7 and 4 years old, respectively. Renal biopsy revealed proliferative glomerulonephritis, resembling MPGN type III. The family history showed that their father and grandfather suffered from end-stage renal disease, suggesting that MPGN seen in the present sibling cases is hereditary. A review of the literature revealed that familial MPGN is rare, that most of the cases have urinary abnormalities at an age of less than 10 years, and that male preponderance is seen in familial MPGN.     

Mesangial glomerulopathy in rheumatoid arthritis patients. Clinical follow-up and relation to antirheumatic therapy

23 patients (16 women, 7 men) with rheumatoid arthritis (RA) and renal biopsy-proven mesangial glomerulopathy (MGP) were followed for 4-117 months (median 42) in order to evaluate the clinical course of their renal disease. Urinalysis was made, and 24-hour urine protein excretion and serum creatinine were determined. At the time of renal biopsy, the clinical renal findings of the patients were isolated hematuria (n = 10), isolated proteinuria (n = 6) and hematuria combined with proteinuria (n = 7). Hematuria persisted and renal function remained normal in all patients with isolated hematuria. A possible association between the presence of hematuria and the use of antirheumatic drugs was not established in this study. Proteinuria was clinically closely associated with the use of antirheumatic drugs in 9 out of 13 cases (6 with gold sodium thiomalate, 2 with D-penicillamine and 1 with auranofin) suggesting that antirheumatic drugs are important contributors to proteinuria in these patients. Renal function, although initially reduced in some patients, remained stable in all but 1 patient with IgA glomerulonephritis who developed the nephrotic syndrome and died of uremia. In conclusion, the clinical course of MGP in RA patients is benign in most patients. Moreover, this nephropathy may not represent a clinical entity. Proteinuria was related to antirheumatic drugs in most patients whereas microhematuria was constant even after stopping the antirheumatic drugs.