Francisco Mampaso

Membranoproliferative Glomerulonephritis and Hepatitis C Virus Infection

Ana Gonzalo, MD, Servicio de Nefrología, Hospital Ramón y Cajal, Carretera de Colmenar, Km. 9,100, E-28034 Madrid (Spain) Fig. 1. Glomerulus showing increased number of mesangial cells and matrix. HE. × 400. remained raised at 100 U/1 and a liver biopsy showed active chronic hepatitis. A severe mononuclear cell infiltrate was observed in the portal tracts with rupture of the limiting plate (piecemeal necrosis). Ground glass he-patocytes were absent and liver architecture was conserved. Three months later, proteinuria and microhematuria persisted unchanged and a renal biopsy was performed. It contained five glomeruli, all of them showing diffuse mesangial cell proliferation and an increased mesangial matrix. Accentuation of the glomerular lobular pattern as well as peripheral mesangial cell interposition was also observed (fig. 1). Presence of Dear Sir, Membranoproliferative glomerulonephritis (MPGN) with subendothelial deposits (type I) is a well-defined clinicopathological entity [1] which although it may be associated with several conditions [2], is usually idio-pathic. Many cases of GN related to chronic hepatitis B virus (HBV) infection have been classified as MPGN and the etiologic role of HBV in MPGN has been considered. Rollino et al. [3] have recently described the association of hepatitis C virus (HCV) infection and membranous nephropathy, stressing the importance of systematic research of HCV antibodies in order to identify one more causal factor of this nephropathy. We present a patient with HCV infection and type I MPGN. A 28-year-old previously non transfused woman, consulted her physician in September 1990 because of asthenia, anorexia and weight loss during the preceding month. She did not have arthralgias, Raynaud’s phenomenon or cutaneous lesions. On physical examination blood pressure was 130/80 mm Hg, the liver was not palpable and she did not have edema. Analytical studies disclosed serum creatinine 0.7 mg/dl, proteinuria 19 mg/ kg/day and urine red blood cells 375,000/ min with hyaline and hyaline-granular casts. Alanine aminotransferase (ALT) was 649 U/ 1, total serum bilirubin 0.9 mg/dl, serum albumin 32 g/l and total protein 62 g/l. Serum IgG and IgA levels were in the normal range (1,070 and 113 mg/dl, respectively) and IgM was 348 mg/dl (normal 70-280 mg/dl). Serum complement

Hypertension in primary chronic glomerulonephritis: analysis of 288 biopsied patients

The prevalence of hypertension in 288 patients with primary chronic glomerulonephritis was compared with that observed in a control group of 3,477 subjects from the same geographic area. 23.3% of the patients and 12.8% of the general population were hypertensive (p less than 0.01). However, if only patients with normal renal function were considered, prevalence of hypertension (12.7%) was not higher than in the control group. Hypertension was more frequent in focal segmental sclerosis (30%) and in membranous glomerulonephritis (26%) than in IgA nephropathy (9%), membranoproliferative glomerulonephritis (11%) and IgM mesangial glomerulonephritis (12%). Five years after renal biopsy, 92% of normotensive and 47% of hypertensive patients remained with normal renal function (p less than 0.001). These findings suggest that the high prevalence of hypertension in chronic glomerulonephritis is related to the declining renal function. On the other hand, hypertension appears to represent a bad prognostic sign.

Clinical Significance of IgM Mesangial Deposits in the Nephrotic Syndrome

We have studied 32 patients with idiopathic nephrotic syndrome aged from 3 to 59 years. The clinical course of 20 patients with IgM mesangial deposits was compared with that of 12 patients without glomerular immune deposits. The presence of IgM deposits seems to be unrelated to any particular clinical onset, histological pattern on light microscopy, therapy response, or clinical course in our relatively short follow-up. The conclusion from this study is that IgM mesangial deposition is not a marker for response to therapy in patients with idiopathic nephrotic syndrome.

Familial C1q Deficiency in 3 Siblings with Glomerulonephritis and Rothmund-Thomson Syndrome

Complete absence of C1q was demonstrated in the sera of 3 siblings in association with renal and cutaneous lesions. The serologic findings were consistent with an autoimmune disorder. Hematuria was the renal symptom present in all 3 patients; proteinuria was also present in 1. Renal biopsies showed mesangial proliferative glomerulonephritis with diffuse glomerular deposits of IgM and C3 in all cases. Clinical cutaneous manifestations and the histological picture were those of the Rothmund-Thompson syndrome. Three combined diseases, characterized by renal and cutaneous affection and serologic abnormalities, are presented in this paper.

Acute interstitial nephritis superimposed on glomerulonephritis: report of a case

A 7-year-old boy with a history of recurrent acute renal failure and macroscopic haematuria is reported. A renal biopsy performed during the first episode of renal function deterioration showed mesangial glomerulonephritis with C3 mesangial deposits. Macroscopic haematuria associated with respiratory infections recurred four times over the next 14 months, each time in association with acute derangement of renal function. A second biopsy showed acute interstitial nephritis and similar glomerular abnormalities. Retrospectively, a causal relationship between the ingestion of paracetamol and the appearance of the symptoms was observed. No derangement of renal function was present in subsequent episodes of macroscopic haematuria following removal of the offending drug. This is a case of drug-induced acute interstitial nephritis superimposed on a glomerular disease, and suggests the importance of recognizingthis association.

Acute Interstitial Nephritis Induced by Ethambutol

Dr. Florencio García-Martín, C/Sangenjo 9, 6 A, E-28034 Madrid (Spain) Dear Sir, Drug-induced acute interstitial nephritis is recognized with increasing frequency with antibiotics, diuretics and nonsteroidal anti-inflammatory agents being the more commonly implicated drugs [1]. We report here an unusual case of acute renal failure secondary to ethambu-tol-induced acute interstitial nephritis. A 58-year-old woman was admitted with asthenia, anorexia, weight loss and episodes of macroscopic hematuria. Blood pressure was 170/102 mm Hg, hemoglobin 13.8 g/dl with a normal white blood cell count and an erythrocyte sedimentation rate of 90 mm/h; BUN 44 mg/dl (15.7 mmol/l), plasma creatinine 2 mg/dl (177 μmol/ 1), total serum protein 6.9 g/dl (69 g/l) and albumin 3.4 g/dl (34 g/l). Urinalysis protein was 2.5 g/24 h, 15–20 erythrocytes pmf and 20–25 leukocytes pmf. Urine cultures were negative; Mycobacterium tuberculosis bacilli were identified (Löwenstein) in the urine. She was immediately started on antituberculous treatment: Rifampin 10 mg/ kg/day, isoniazid 5 mg/kg/day and ethambutol 15 mg/kg/day. The patient was readmitted to hospital 5 weeks later with fever and generalized cutaneous papuloerythematous lesions as well as oral vesicles. Blood pressure was 150/80 mm Hg; laboratory data at that time revealed a hemoglobin level of 11.3 g/dl with a white blood cell count of 8.3×10V1 (eosinophils 0.9×10V1), BUN 118 mg/dl (42.1 mmol/l), plasma creatinine 4.6 mg/dl (407 μmol/l), total serum protein 6.6 g/dl (66 g/l), albumin 3.2 g/dl (32 g/l). Serum Ig and C values were within normal ranges. The urinary volume was 1.5 liters/day with a urinary protein excretion of 3.5 g/24 h, microhe-maturia and abundant white blood cells. Fractional excretion of sodium 3.1%. An open kidney biopsy was done showing advanced glomerular sclerosis and a intense interstitial mononuclear cell infiltrate with a discrete degree of interstitial fibrosis. Direct immunofluorescence studies showed no Ig and/or C deposits in the kidney tissue. Treatment with rifampin and isoniazid was stopped, and treatment with prednisone (45 mg/day) was initiated. Three weeks later, and due to the persistence of clinical manifestations as well as renal insufficiency, the administration of ethambutol was suspended. After 2 weeks, the cutaneous lesions disappeared and improvement of renal function was noted with BUN 50 mg/dl (17.8 mmol/l) and creatinine 2.1 mg/dl (186 μmol/l). The patient was PRED PZM RFP

Thrombotic Microangiopathic Nephropathy in Scleroderma and Lupus Anticoagulant

A 47-year-old woman with overlap scleroderma-polymyositis syndrome and positive circulating lupus anticoagulant developed scleroderma nephropathy, characterized by rapidly progressive renal failure caused by thrombotic microangiopathy with widespread thrombi in small arteries and glomeruli. The possible relationship between lupus anticoagulant and the development of thrombosis at the small renal vessels level with the triggering of the scleroderma crisis is discussed.

RECURRENCE OF FOCAL-SEGMENTAL GLOMERULOSCLEROSIS IN KIDNEY TRANSPLANT PATIENTS ON CICLOSPORIN

Two patients on maintenance hemodialysis after terminal renal failure due to nephrotic syndrome and biopsy-proven focal-segmental glomerulosclerosis received three cadaver renal allografts. Immediate recurrence of nephrotic syndrome was observed. In two transplants immunosuppression consisted of ciclosporin A and low-dose steroids. One patient was unsuccessfully treated with immunoadsorption after the second transplant. All grafts were lost because of uncontrolled nephrotic syndrome. Renal allograft biopsy specimens showed findings indicating recurrence of the original disease.

Recurrence of IgA Nephropathy with Nephrotic Syndrome after Kidney Transplantation

Two patients on maintenance hemodialysis after terminal renal failure due to mesangial glomerulonephritis with IgA deposits and the nephrotic syndrome, received cadaver renal allografts. After several years of functioning transplants, both patients developed slowly progressive proteinuria and finally the nephrotic syndrome, 1 of them with renal function deterioration. Renal biopsies revealed findings indicating recurrence of the original disease.

Steroid-Responsive Nephrotic Syndrome with IgA Deposits

A. Gonzalo, Servicio de Nefrología, Hospital Ramón y Cajal Carretera de Colmenar, Km. 9,100, 28034 Madrid (Spain) Dear Sir, Several recent reports have focused attention on cases of steroid-responsive nephrotic syndrome (NS) in association with IgA glomerular deposits. The precise classification of these patients is at present controversial [2, 3, 6]. Those previously reported cases have similar clinical and histologic features as most of them were children with minimal change lesions. However, this condition has also been considered a rare variant of IgA nephropathy [4], minimal lesion nephrosis with IgA mesangial deposits [5] or the coincidence of two glomerular diseases where IgA nephropathy has superimposed on minimal change NS [1]. We present a patient with steroid-responsive NS and mesangial IgA deposits showing ‘early’ lesions of focal glomerular sclerosis. A 20-year-old man developed edema on October 2,1985, without a previous history of infection. Blood pressure was 150/85 mm Hg, serum creatinine 1 mg/dl, proteinuria 92 mg/kg/day and urine red blood cells 8,000/min. Serum albumin was 26 g/l and total protein 43 g/l. Cryoglobulins, antinuclear antibodies and HBsAg were negative. The serum C3, C4 and CH50 were normal. IgA levels were not raised (97 mg/dl), IgG 420 mg/dl and IgM 107 mg/dl. The patient received a salt-restricted diet and diuretics. A percutaneous renal biopsy showed 29 glomeruli. On light microscopy 3 were sclerosed and another 2 showed focal and segmental glomeruloscle-rotic lesions (fig. 1). The rest exhibited irregular mesangial hypercel-lularity with a mild increase in mesangial matrix. There were small foci of interstitial fibrosis and tubular atrophy. Immunofluores-cence disclosed generalized and diffuse mesangial deposits of IgA (2 + ) and C3 (1+). Electron microscopy showed no evidence of electron-dense deposits in the glomerular basement membrane or in the mesangium. On October 27, 1985, proteinuria was negative, serum albumin rose to 36 g/l and total serum protein went up to 63 g/l. Three weeks later, a second attack of NS was present with edema and proteinuria 72 mg/kg/day. Serum albumin dropped to 28 g/l, hematuria was not detected and renal function remained normal. Treatment with 1 mg/kg/day of prednisone was started; proteinuria disappeared on the 15th day. On the last examination, 3 months after prednisone withdrawal, the patient was asymptomatic and proteinuria was not present. We think that our patient has an idiopathic NS with IgA mesangial deposits and not IgA nephropathy (Berger’s disease). It is known that IgM deposits may appear in some cases of nephrosis, most probably as a consequence of secondary trapped proteins in previously injured