Primary systemic amyloidosis: resolution of the nephrotic syndrome with melphalan and prednisone.

We describe two patients with primary systemic amyloidosis (AL) and the nephrotic syndrome. The administration of melphalan and prednisone was associated with resolution of the nephrotic syndrome. The serum albumin level returned to normal, proteinuria decreased to near normal, edema resolved, and the monoclonal protein in the serum and urine disappeared. In both patients, renal function remained stable and hepatomegaly disappeared. In both, however, amyloid deposition was greater in follow-up renal tissue than in the initial specimen. The effect of systemic therapy in AL must be assessed with histologic observations as well as clinical indexes.

Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy.

The aims of this study were to examine in a prospective, randomized trial the efficacy of plasmapheresis in preventing irreversible renal failure in patients with multiple myeloma and to study the renal biopsy tissues from such patients. Twenty-one patients with active myeloma and progressive renal failure were randomized to one of two groups: group 1, forced diuresis and chemotherapy (10 patients), and group 2, forced diuresis, chemotherapy, and plasmapheresis (11 patients). Plasmapheresis and chemotherapy lowered the serum myeloma protein value much more rapidly than chemotherapy alone. Of 5 patients who were oliguric and undergoing dialysis at presentation, only 3 who were treated by plasmapheresis recovered. Of 16 polyuric patients, 5 in group 1 and 7 in group 2 showed improvement in renal function. The main factor that determined irreversibility of renal failure was the severity of myeloma cast formation.

Membranous lupus nephropathy: a clinicopathologic study.

Twenty-eight patients with SLE and distinct, well-defined renal morphologic lesions of membranous nephropathy were followed up for 4 years. These patients comprised approximately 8% of the patients evaluated for SLE during a 12-year period. The patients with membranous lupus nephropathy had typical systemic features of SLE, and most of them had positive LE cell tests and ANA, low serum complement concentrations, and mildly elevated serum antinative DNA levels. Proteniuria and microscopic hematuria were usually discovered years after systemic symptoms of SLE had developed, Only two patients had slowly progressive renal failure, and most patients continued to have proteinuria. Prednisone treatment did not influence either proteinuria or renal function. In only one patient, the renal character of the disease changed drastically, demonstrating membranoproliferative glomerulonephritis. Six patients died (21%); most of these died of cardiovascular illnesses. The relatively benign and stable renal course of membranous lupus nephropathy in patients with otherwise typical SLE suggests that the renal pathogenesis is different from that of proliferative lupus nephritis.

Renal involvement in relapsing polychondritis.

Twenty-nine of the 129 patients with RP seen at the Mayo Clinic between 1943 and 1984 had renal involvement. These patients were older, had arthritis and extrarenal vasculitis more frequently, and had a significantly worse survival rate than those without renal involvement. Renal biopsies were obtained in 11 of these 29 patients. The predominant lesions were mild mesangial expansion and cell proliferation, and segmental necrotizing glomerulonephritis with crescents. Small amounts of electron-dense deposits, predominantly mesangial, were noted on electron microscopy. Immunofluorescence revealed faint deposition of C3 and/or IgG or IgM, predominantly in the mesangium. Autopsies were obtained in 13 of the 47 patients who had died. Information regarding the renal pathology was available in 10 of these 13 autopsies. At the time of the initial evaluation at the Mayo Clinic, 6 of these 10 patients had evidence of renal involvement. At autopsy, none of these 10 patients had evidence of active renal vasculitis or segmental necrotizing glomerulonephritis, but 8 of the 10 patients exhibited variable degrees of vascular and glomerular sclerosis, segmental mesangial proliferation, tubular loss, and interstitial lymphocytic infiltrates. These observations expand the limited information available in the literature, which is based on 11 previously published case reports of renal involvement in RP. In only a few of our patients and previously reported patients were the manifestations of the disease limited to the systems characteristically involved in pure RP. The frequent coexistence of other autoimmune and connective tissue diseases supports the role of immune mechanisms in the pathogenesis of this syndrome. Deposition of immune complexes is likely to play a role in the pathogenesis of the glomerular lesions associated with RP. Administration of corticosteroids alone is sufficient to induce a complete remission in some cases, while in others the addition of a cytotoxic agent is necessary to control the activity of the disease or to spare corticosteroid side effects and maintain a remission. Immunosuppression-related infectious complications and undetected relapses after discontinuation of immunosuppressive therapy are largely responsible for the morbidity and mortality observed in these patients.

Fanconi syndrome in adults. A manifestation of a latent form of myeloma.

From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.

In vitro alteration of canine renal allograft immunogenicity.

Significant prolongation of renal allograft survival was demonstrated in a controlled canine model with the host suboptimally immunosuppressed when grafts were perfused for 24 hr with cryoprecipitated plasma (CPP) that had been obtained from plasma of dogs "pretreated" with i.v. cyclophosphamide (80 mg/kg for 5 1/2 hr) and i.v. methylprednisolone (60 mg/kg for 2 1/2 hr). The active metabolites of these drugs within the pretreated plasma may have modified the graft immunogenicity in vitro. However, the use of pretreated kidneys in combination with 24 hr of perfusion with CPP did not result in prolonged graft survival. Furthermore, 24-hr perfusion of pretreated kidneys with their own pretreated CPP did not improve graft survival. This suggests that the pretreated canine kidney does not tolerate pulsatile preservation with CPP; this is in contrast to the human experience and may be attributable to a species difference.

Immunological donor pretreatment in combination with pulsatile preservation in cadaveric renal transplantation.

The extended experience on the efficacy of pretreating the cadaveric renal allograft donor by means of large doses of cyclophosphamide and methylprednisolone (group A, 36 kidneys) was compared with the experience regarding untreated renal allografts (group B, 32 kidneys). Kidneys in both groups were perfused by pulsatile means using cryoprecipitated plasma. There was a significant difference in allograft survival (72% in group A versus 36% in group B at 3 years by actuarial means). Also, large doses of cyclophosphamide and methylprednisolone as pretreatment did not cause any detrimental effect to the allograft kidney when used in combination with cryoprecipitated plasma and pulsatile perfusion.

Eosinophil granule major basic protein in acute renal allograft rejection.

Conventional staining techniques to determine the presence of tissue eosinophils underestimate their number and do not usually detect eosinophil degranulation. We have studied the involvement of eosinophils in acute renal allograft rejection by immunofluorescence localization of eosinophil granule major basic protein (MBP) in the kidney and by measurement of MBP in the plasma and urine by radioimmunoassay. Tissue eosinophilia and extracellular deposition of MBP indicative of eosinophil degranulation were observed in 94% and 87%, respectively, of patients with acute rejection as compared with 17% and 17%, respectively, of patients with cyclosporine nephrotoxicity. The urine levels of MBP were significantly elevated in acute rejection but not in cyclosporine nephrotoxicity. Plasma MBP concentrations were within the normal range in both acute rejection and cyclosporine nephrotoxicity. The presence of marked tissue eosinophilia and eosinophil degranulation did not always indicate irreversible rejection. Interleukin-2 and IL-2 receptors were also elevated in the urine during acute rejection. These results support a role for the eosinophil as an effector of tissue damage during rejection and suggest the potential usefulness of urine MBP determinations for the immunologic monitoring of transplanted patients.

Renal transplantation in Alport's syndrome: anti-glomerular basement membrane glomerulonephritis in the allograft.

Eleven patients with Alport's syndrome had renal transplantation between 1963 and 1980. The mean follow-up is 6 years (6 months to 14 years). All 11 patients are currently alive. Ten have functioning grafts, and in nine the serum creatinine concentration is less than 2 mg/dl. Three patients received a second allograft. Histologic study of the allografts that were lost revealed a diffuse crescentic glomerulonephritis with strongly positive linear IgG staining of the glomerular basement membrane in the allografts of two of the three patients; circulating antiglomerular basement membrane antibodies were present in one patient. These two patients had successful retransplantation and they remain well 1 1/2 and 4 1/2 years later. Renal transplantation in patients with Alport's syndrome is a worthwhile and very satisfactory procedure.

Renal failure associated with fenoprofen.

The nonsteroidal anti-inflammatory drugs used in treating various arthritides have been implicated in decreased renal function. We describe two patients who had acute renal failure that was apparently secondary to fenoprofen and was associated with a tubulointerstitial nephritis and nephrotic syndrome. The complication resolved when the use of the drug was discontinued.

Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis.

We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis.

Effect of intrahepatically implanted islets of Langerhans on hepatic function in the rat.

Diabetes mellitus is satisfactorily controlled in the rat by hepatic implantation of isolated, isologous pancreatic islets. The transplanted islets appear to be viable for at least 6 months after implantation, and hepatic function studies (serum bilirubin, alkaline phosphatase, glutamic-oxalacetic transaminase, prothrombin time) and microscopic examination indicate that they do not interfere with hepatic function.

Focal sclerosing glomerulonephropathy: a clinicopathologic study.

Forty cases of focal sclerosing glomerulonephropathy with nephrotic syndrome or proteinuria were studied retrospectively in regard to clinical presentation, response to steroid therapy and clinical course, and histopathology of the lesion. Morphologically there was a focal segmental and global sclerosis with subendothelial hyaline deposits, collapse of the capillary loops, intracapillary hyaline material or foam cells, filling and widening of the mesangium with mesangial matrix, focal tubular atrophy, and focal interstitial fibrosis. Thirty-four patients had been treated with prednisone; initial complete remission of the nephrotic syndrome occurred in only 4 patients and partial remission in 10. Nine of these 14 patients had nephrotic relapse or became resistant to steroids. Thirty-three percent of the patients progressed to end-stage renal failure and an additional 25 percent had impairment of renal function after a mean of 8 years from onset. Three patients received kidney allografts, and in two the disease recurred in the transplanted kidney. Focal sclerosing glomerulonephropathy associated with nephrotic syndrome or proteinuria appears to be a clinicopathologic entity characterized by resistance to steroid treatment, frequent progression to end-stage renal disease, and recurrence in the transplanted kidney.

Class of immunoglobulin deposition and prognosis in lupus nephritis.

In the three major morphologic groups of lupus nephritis--diffuse, focal proliferative, and membranous--glomerular deposition of immunoglobulins is usually a combination of IgG, IgM, and IgA and is not a good indicator of initial renal severity or outcome. In this study of 60 patients with systemic lupus erythematosus and nephritis, patients with exclusive or predominant glomerular deposition of IgG did not have more severe renal disease or a worse prognosis than those with combined IgG-IgM deposition.

Mesenteric angiofollicular lymph node hyperplasia (lymphoid hamartoma) with nephroitc syndrome.

In an 18-year-old woman who presented with the nephrotic syndrome and an abdominal mass, removal of a benign mesenteric lymphoid tumor was associated with remission of the nephrotic syndrome without further recurrence (30 month follow-up). Biopsies of both kidneys showed a minimal-change glomerular lesion. Clinical and pathologic characteristics of angiofollicular lymph node hyperplasia and its possible relationship to the nephrotic syndrome are discussed.

Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis: a clinicopathologic study.

In 51 patients with type 1 and 9 patients with type 2 membranoproliferative glomerulonephritis, we found a male predominance in both types, a wide age range but with younger patients having predominantly type 2 disease, and clinical presentations that varied and included the nephrotic syndrome, an abnormal urinalysis only, acute nephritis, and recurrent hematuria. Hypertension and impaired renal function at the time of first evaluation, which were present in more than one-third of the patients, presaged a poor prognosis; in most of these patients end-stage renal failure or worsening of renal function occurred. Acute nephritis at onset was also related to a deteriorating course and was especially frequent in patients with type 2 membranoproliferative glomerulonephritis. Retrospective analysis of treatment regimens, in which patients were given an average of 1 year of therapy with prednisone alone or combined with cytotoxic agents, showed no effect in patients who had progressive forms of the glomerulopathy.

Isolated renal artery dissection, presentation, evaluation, management, and pathology.

Isolated nontraumatic renal artery dissection is rare. In this communication, 35 cases are presented; 24 cases (group 1) (22 male, 2 female) were diagnosed angiographically, and 11 (group 2) (10 male, 1 female) were observed at autopsy. In group 1, 23 of the patients were hypertensive when they were first seen, and in 17 of them the hypertension was of recent onset. Additional presenting signs and symptoms included flank pain (10 patients), gross hematuria (5), and headaches (6). Renal function was satisfactory. Renal vein renin levels could be lateralized in 8 of 16 patients. Isotope renograms performed in 18 patients, showed unilateral abnormalities in 7, bilateral abnormalities in 6, and normal results in 5. Angiograms showed that the dissection was unilateral in 18 cases and bilateral in 6 cases. Fibromuscular dysplasia was observed radiographically in 22 cases and was bilateral in 12. In group 1, 13 patients were treated with antihypertensive medication only, and 11 underwent operation. At follow-up (mean 52.0 months), the mean blood pressure were 128/88 mm Hg and 139/89 mm Hg for the medical and surgical groups, respectively. Eleven medical and nine surgical patients continued to require antihypertensive drugs at follow-up. Among the 11 patients in group 2, only 4 were hypertensive. In only one case the dissection may have contributed significantly to the patient's death. These studies indicate that isolated nontraumatic renal artery dissection most commonly occurs in young men with coexistent fibromuscular dysplasia. Hypertension is commonly present and therapy should be directed toward its control. In this study, blood pressure control was effectively accomplished with medical therapy.

Immunologic mechanisms in systemic vasculitis.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.

Progressive lupus glomerulonephritis. Treatment with prednisone and combined prednisone and cyclophosphamide.

We report a prospective randomized study of 39 patients with systemic lupus erythematosus and progressive glomerulonephritis who were assigned to treatment groups that received either prednisone alone or prednisone and cyclophosphamide combined. They received treatment for 6 months and were then followed up for an additional 18 months. No difference in outcome was seen in the two groups at the end of 6 months. Among patients followed up for an average of 24 months, fewer individuals showed later renal progression among those treated with cyclophosphamide and prednisone than among the group treated with prednisone alone.

Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients.

Between 1978 and 1988, three patients at our institution had an initial diagnosis of idiopathic pulmonary fibrosis but later were correctly diagnosed as having pulmonary-renal syndrome and microscopic polyarteritis. These cases involved elderly patients with progressive dyspnea and nonproductive cough, bilateral dry crackling rales, bilateral interstitial infiltrates evident on a chest roentgenogram, and restrictive findings on pulmonary function testing. In two patients, lung biopsy specimens were obtained, and an initial diagnosis of nonspecific pulmonary fibrosis was made. All three patients eventually had microhematuria and renal insufficiency. A revised diagnosis of small-vessel pulmonary-renal vasculitis was based on the demonstration of segmental necrotizing glomerulonephritis in renal biopsy specimens in two patients, thrombotic microangiopathy consistent with healed vasculitis on postmortem examination of the kidney in one patient, and subsequent detection of small-vessel vasculitis on review of the two lung biopsy specimens. Anti-neutrophil cytoplasmic antibodies with perinuclear staining on indirect immunofluorescence microscopy were positive in the two patients in whom determinations were performed. The clinical manifestations of vasculitis were notably scarce--no involvement of the skin, nervous system, or gastrointestinal tract; no episodes of fever; and minimal or absent musculoskeletal symptoms. These cases illustrate the importance of a high index of suspicion for the diagnosis of systemic vasculitis in elderly patients and the need to consider a vasculitis in the differential diagnosis of idiopathic pulmonary fibrosis, especially if an active urinary sediment is present.