MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS WITH IgM DEPOSITION: CLINICAL CHARACTERISTICS AND OUTCOME

The significance of IgM on immunofluorescence in renal biopsy specimens remains unclear. This retrospective case study was conducted to define the clinical features, response to therapy and outcome of patients with Mesangioproliferative Glomerulonephritis (MGN) with diffuse IgM deposition. Of 1919 native renal biopsies performed over a ten-year period, 139 (7.2%) had light microscopic features of MGN and manifested IgM as the dominant immunoglobulin. When exclusion criteria (more than a trace of IgA or IgG, segmental IgM, evidence of SLE, vasculitis, FSGS or Alport's syndrome and pregnant patients) were applied, 60 patients (3.1%) remained. Follow-up data were available for 54 cases with a mean age of 26.5 years (range 1.7–63). Mean follow-up period was 7.4 years (range 4.7–22.2). Forty-one per cent presented with nephrotic syndrome (NS), 26% with asymptomatic proteinuria (>250mg/24hr), 18% with macroscopic hematuria and 15% with isolated microscopic hematuria. Twenty-one percent of patients were hypertensive at presentation. Creatinine was initially <120(mol/L in all but one patient. Only four patients (7.4%), all nephrotic, suffered a decline in renal function despite treatment; all 4 developed ESRF after a mean of 5.6 years (range 2–8.3). Two of these were subsequently re-biopsied and found to have FSGS. No patients with isolated microscopic / macroscopic hematuria or asymptomatic proteinuria suffered a decline in renal function. Protein excretion rate fell into the normal range in 63% of those receiving steroids, with 82% becoming steroid dependent. Of those treated with cyclosporine (48%) or cyclophosphamide (52%) only 9.5% and 14.5% respectively remained in prolonged remission after discontinuing treatment. It is concluded that MGN with IgM deposition carries a very favorable prognosis except in patients with NS who develop FSGS. However there is a high incidence of steroid dependence and resistance in the proteinuric group.     

The Prognosis of Renal Vein Thrombosis: A Re-evaluation of 27 Cases

Twenty-seven patients with renal vein thrombosis were retrospectivelystudied to evaluate their long-term prognosis and relevant prognosticfactors. Twenty-four patients presented with a nephrotic syndrome, and15 had renal impairment (8 acute; 7 moderate). Ten patientshad a previous history of proteinuria, and 14 of nephrotic syndrome.Renal biopsy performed in 20 patients, of whom 19 were nephrotic,showed membranous glomerulonephritis in 14, focal segmentalglomerulosclerosis in three, minimal change glomerulonephritisin two, and periarteritis nodosa in one. Renal vein thrombosiswas angiographically proven in all patients and was bilateralin 18, localised to the left renal vein in seven, and to theright in two. Thrombosis of the inferior vena cava was associatedin seven patients. Ten patients were treated by anticoagulants alone, nine by surgicalthrombectomy, seven by thrombolysis, and two did not receiveany specific treatment. One patient underwent successively thrombectomyand then thrombolysis. Eleven patients died within the first6 months, mainly from haemorrhagic complications (n = 5) orsevere sepsis (n = 2). Survivors were followed up from 6 monthsto 19 years. Nephrotic syndrome improved or even disappearedin 12 patients, and renal function did not worsen throughoutthe follow-up in any patients. The main prognostic factors were initial renal function andtype of nephropathy: patients with membranous glomerulonephritishad a significantly better renal function and a lower mortalityrate than patients with other nephropathies. Initial renal insufficiencywas significantly associated with a poor prognosis. There wasno advantage, in terms of survival, kidney function and nephroticsyndrome, of either thrombectomy or thrombolysis over anticoagulantsalone, despite two complete venous recanalisations after thrombolysis. Accordingly, patients with renal vein thrombosis from membranousglomerulonephritis should be treated by anticoagulants alone,since the long-term prognosis of this disease seems unaffectedby intercurrent renal vein thrombosis. With respects to therisk-to-benefit ratio, thrombectomy should be avoided and thrombolysisconsidered only in patients with initial acute renal failurefrom acute renal vein thrombosis.     

Acute reversible renal failure with macroscopic haematuria in IgA nephropathy

Macroscopic haematuria is common in IgA nephropathy, but itssignificance and influence on prognosis remains uncertain. Wecompared the clinical and pathological features of 11 adultpatients with primary IgA nephropathy who had had a renal biopsyduring or shortly after a bleeding episode. Six patients developedtransient acute renal failure (ARF) (group 1) and five did not(group 2). Patients of group 1 had a higher percentage of tubularred-blood-cell (RBC) casts (P<0.05) and of glomerular crescents(P<0.001). However, crescents were focal and involved lessthan 50% of glomeruli. Acute tubular necrosis was only presentin patients of group 1, and ARF was attributed to the acutetubular changes rather than to the glomerular lesions. Despitea prolonged duration of ARF (mean: 38 days), further outcomedid not differ in patients of both groups. We suggest that acutetubular damage and/or tubular obstruction by RBC casts shouldbe considered in any patient who develops ARF soon after a haematuricepisode.     

Splenic Marginal Lymphoma and Glomerulonephritis: Case Report and Review of the Literature

Malignant lymphomas can affect kidneys in several ways. They may precipitate acute renal failure by causing ureteral or renal vascular obstruction, or by direct renal parenchymal infiltration. Furthermore, they may insult renal function via paraneoplastic mechanisms such as hypercalcemia. Lymphomas only rarely can cause glomerulonephritis (GN). We report a case of a 72-year-old male who presented with mild renal function impairment, proteinuria, and microscopic hematuria, suggesting active glomerulonephritis, and pancytopenia of immune origin. A bone marrow biopsy led to a diagnosis of splenic marginal zone lymphoma. Although a kidney biopsy was not performed, glomerulonephritis was attributed to the lymphoma and splenic marginal zone lymphoma-related glomerulonephritis was the final diagnosis. The course of splenic marginal zone lymphoma is extremely indolent. The first manifestation in some patients can be immune cytopenia or other autoimmune phenomena. These patients may respond well to corticosteroids. Therefore, our patient was started on prednisolone resulting in a good hematologic response. Renal function also improved and proteinuria and hematuria disappeared, suggesting a lymphoma-related origin of the GN. Two years after full steroids withdrawal, the patient remained stable with a good renal function and daily protein excretion less than 300 mg. Lymphomas rarely are the cause of secondary glomerulonephritis; however, with a lack of an apparent cause, the clinician should be aware of them, particularly in the elderly with autoimmune manifestations.     

Acute renal failure during pregnancy--an unusual cause.

Post-infectious glomerulonephritis as a cause of acute glomerulardisease and renal failure during pregnancy has been rarely reported.We report a patient with acute glomerulonephritis during thesecond trimester of an otherwise uncomplicated pregnancy, whopresented with acute renal failure (ARF), the diagnosis of whichwas confirmed by renal biopsy.

The Spectrum of Adult Postinfectious Glomerulonephritis in the New Millennium

Background. Postinfectious glomerulonephritis is rare in adults. The characteristics of the disease now differ from what were described decades ago. The goal of this study is to illustrate the clinicopathological spectrum of the disease in the modern era. Methods. Between July 2000 and June 2008, 20 adult cases of postinfectious glomerulonephritis were identified at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. Results. There were 14 males and 6 females. The mean age was 61 years. All patients developed acute renal failure, and the majority (65%) required dialysis support during the disease course. Hypocomplementemia was present in 60% of patients. The most frequently identified infectious agent was Staphylococcus (60%). Histological characteristics showed two distinct patterns of glomerulonephritis: diffuse endocapillary proliferative glomerulonephritis (65%) and focal mesangial proliferative glomerulonephritis (35%). There were no significant differences in the clinical presentation and outcome between the two groups. However, glomerular neutrophil infiltration was more commonly present in diffuse endocapillary proliferative pattern (p = 0.017). The percentage of patients with focal mesangial proliferative pattern significantly increased over time (p < 0.001). At the last follow-up, 6 patients (30%) had died, 6 (30%) were in complete remission, 4 (20%) had partial remission with renal insufficiency, and 4 (20%) were on chronic dialysis. Conclusions. Our data suggested that Staphylococcus had become the leading pathogen in adult postinfectious glomerulonephritis over the past 10 years. Furthermore, atypical histological feature with focal mesangial proliferative pattern was increasingly identified over time. The prognosis was still guarded, carrying a considerable mortality rate and risk for developing chronic renal failure.     

PRIMARY INTESTINAL HODGKIN'S DISEASE COMPLICATING ILEAL CROHN'S DISEASE

An unusual primary intestinal lymphoma that occurred as a complication of ileal Crohn's disease is presented. Immunohistochemistry confirmed the light microscopic diagnosis of Hodgkin's disease (nodular sclerosing), and characterized a distinct mucosal nodule as a large-cell anaplastic non-Hodgkin's lymphoma. This unusual lymphoma developed while the patient was being treated with immunosuppressant medication. The present report is a reminder to clinicians of the possibility of occult lymphoma in ileal Crohn's disease.     

Multiple Renal Cystic Lesions and Acute Renal Failure in Non-Hodgkin's Testicular Lymphoma—A Case Report

To evaluate renal function after the use of a low-osmolality radiological contrast medium (CM), we prospectively analyzed 39 patients submitted to the following examinations: arteriography (n = 32), phlebography (n = 3), computed tomography (n = 3), angioplasty (n = 1), and retrograde pyelography (n = 1). The patients were divided into three groups: group 1, control, formed by renal donors (CT, n = 11 and 11 exams); group 2, hypertensive patients (HYPT, n = 15 and 16 exams): and group 3, patients with diseases of multiple etiologies (MIX, n = 13 patients and 13 exams). Additionally, the patients were divided according to their renal function into: group 4, with a moderate deficit of renal function, creatinine clearance (CrCl) 25 to 60 mL/min (n = 15 patients and 15 exams); and group 5, with a mild deficit of renal function, CrCl ≥ 60 mL/min (n = 14 patients and 14 exams). The CM utilized was ioxaglic acid (Hexabrix) the incidence of acute renal failure (ARF) among the patients studied was 12.5% (5/40), and CrCl was the best parameter to monitor the alterations in renal function, which occurred in 35% of the patients, although the changes were mild, reversible, and did not need any therapeutic interventions. The triggering of ARF in these patients may have been due to multiple factors presented at time of CM examination. Thus, it is not possible to identify a single risk factor. However, it is probable that previous important impairment of renal function was the most expressive risk factor.     

Une étiologie exceptionnelle de l’insuffisance rénale aiguë : le lymphome de Burkitt

IntroductionBurkitt's lymphoma (BL) is an exceptional cause of acute renal failure (ARF). The origin of the tumor clone may be lymphoid follicles secondary to renal Epstein-Barr virus (EBV) infection. With the presentation of this clinical case, the pathogenesis, diagnostic criteria and evolution of this extremely rare affection will be discussed.ObservationA 4-year-old patient with a recent history of acute osteomyelitis of the right thigh presented an ARF without indications of post-infectious glomerulonephritis. Ultrasound showed enlarged kidneys without dilation of the excretory cavities. Diffuse interstitial infiltration of atypical lymphoid cells of medium size were noted upon renal biopsy. The tumor cells expressed antibodies against CD20, CD10, Bcl6, and Ki67 but not against Bcl2 or CD3. The search for an EBV infection was positive. A few days after diagnosis, the evolution was spontaneously fatal.Discussion/conclusionBL of the kidney is a rare condition that accounts for less than 1 % of kidney tumors, associated almost invariably with EBV infection. The diagnosis is confirmed histologically by renal biopsy and the criteria of Malbrain affirms the primitive character of the lymphoma. BL of the kidney is a diagnostic and therapeutic emergency and may be fatal.     

Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies.

BACKGROUND: Based on its success as a transplant immunosuppressor, there is intense interest in using rapamycin in the treatment of progressive glomerulopathies involving native kidneys. However, we call attention to the potential toxicity associated with the use of rapamycin in this setting. METHODS: We conducted a study to examine the efficacy and safety of rapamycin in patients with progressive chronic renal failure. Eleven patients with either focal segmental glomerulosclerosis, immunoglobulin A nephropathy, membranous nephropathy or membrano-proliferative glomerulonephritis and progressive renal failure (defined as an increase in >25% of baseline serum creatinine over the last year or loss of glomerular filtration rate > or =5 ml/min/year as determined by the Cockcroft-Gault formula), proteinuria > or =1.0 g/24 h and with a creatinine clearance of > or 20 ml/min/1.73 m(2) were entered into a 12 month study. Patients were treated with rapamycin, starting at 5 mg/day, orally, aiming for target blood levels of 7-10 ng/dl. All patients were on treatment with an angiotensin-converting enzyme inhibitor and/or an angiotensin receptor blocker, aiming to control blood pressure < or =145/90 mmHg. RESULTS: Six patients developed acute renal failure, defined as an increase in serum creatinine > or =0.5 mg/dl (baseline: 3.2+/-0.9 mg/dl; peak: 5.6+/-1.6 mg/dl; P<0.01, paired t-test). In four patients, discontinuation of the drug resulted in improvement of renal function close to baseline levels. One patient required haemodialysis and had no subsequent recovery of renal function. In another patient, renal function recovered after discontinuation of the drug and then rapamycin was resumed at a lower dose when creatinine returned to baseline. This resulted in a second acute increase in serum creatinine that failed to return to baseline when the medication was discontinued. Four other patients had the following adverse events: skin rash, severe hypertriglyceridaemia, diarrhoea and hyperkalaemia. In none of the subjects were rapamycin levels >15 ng/dl. CONCLUSIONS: Rapamycin can cause nephrotoxicity in some patients with chronic glomerulopathies. Whether the toxicity is solely related to rapamycin, due to the combination of proteinuria and rapamycin, or other unknown factor use is presently undetermined.     

Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction

Seven patients with acute renal failure due to gross haematuriacaused by glomerulonephritis are described. Gross haematurialasting 4–40 days led to acute impairment of renal functionof variable severity (peak plasma creatinine 1.3–12 mg/dl)and duration. While partial recovery of renal function occurredin all patients within few days, complete remission was observedonly some months later. Three patients had IgA nephropathy (2the primary form and 1 nephritis secondary to Schönlein-Henochpurpura), two patients had acute postinfectious glomerulonephritis,andtwo others had focal necrotizing (pauci-immune) glomerulonephritis.The glomerular changes seen in renal biopsy were not enoughto explain per se the renal function impairment. Tubular changes,however, were severe and consisted of tubular necrosis, erythrocytecasts, erythrocyte phagocytosis by tubular cells, accompaniedby interstitial damage (oedema, red-cell extravasation, andinflammatory infiltrates). Study of the renal biopsies by immunofluorescencerevealed retrodiffusion of Tamm-Horsfall protein into the glomerularBowman’s space, a sign of obstructed tubular flow in anycase. It is concluded that acute renal failure due to grosshaematuria in glomerulonephritic patients may not occur onlyin IgA nephropathy, as reported so far, and is not associatedwith intratubular obstruction.     

Comprehensive immunohistological analysis of the endothelin system in human kidney grafts.

BACKGROUND: In experimental models of renal transplantation, upregulation of the endothelin (ET) system and amelioration of renal injury by ET-receptor blockers have been documented. In contrast, little information is available on the expression of the ET system in human kidney allografts. It was the purpose of the present study to analyse by immunohistology the expression of ET-1 as well as of the two ET receptors (ET-RA and ET-RB) in the different cells and compartments of kidney grafts and control kidneys. METHODS: Fifty-five graft biopsies were taken from 55 kidney allograft recipients (mean age: 32+/-2.8 years) who were all on a calcineurin inhibitor. The indication for biopsies was delayed graft function or suspected rejection. The underlying diagnoses were acute allograft rejection (n = 14), chronic allograft nephropathy (n = 14), cyclosporin A (CSA) toxicity (n = 10), post-operative acute tubular necrosis (ATN) (n = 11) and recurrent primary disease (n = 6). As control, tissues of non-grafted kidneys with ATN (mean age: 35+/-24 years), of primary glomerulonephritis (mean age: 69+/-10 years) and of non-tumour-bearing parts of eight tumour nephrectomy specimens (mean age: 67+/-5 years) were assessed. The biopsies were scored using the 1997 Banff criteria. Expression of ET-1, ET-RA and ET-RB as well as of vascular endothelial growth factor was evaluated by immunohistochemistry and a semi-quantitative scoring system. Interstitial infiltrating cells were characterized using antibodies against T cells, B cells and macrophages (CD3, CD20 and CD68). RESULTS: Control cases showed only faint expression of ET-1 in glomeruli (in podocytes and endothelial cells), whereas marked expression was seen in distal, but less in proximal tubular cells. The interstitium was completely negative. ET-1 expression was seen in vascular endothelial cells (VEC) and vascular smooth muscle cells (VSMC). Only faint expression of ET-RA and ET-RB was found in glomeruli and tubuli (distal more than proximal). Marked ET-RA and ET-RB expression was seen in VEC and VSMC. In all transplanted kidneys, irrespective of the underlying diagnosis, expression of ET-1, ET-RA and ET-RB was markedly higher compared with control kidneys. ET-1 was strikingly upregulated in glomeruli and tubuli, but surprisingly not in the vasculature of grafts with CSA toxicity. Expression of ET-RB was markedly increased in CSA toxicity in glomeruli, tubuli and vessels. In grafts with ATN and acute rejection, pronounced expression of ET-RA was noted. There was a strong correlation between proteinuria and expression of ET-1 in glomeruli and proximal tubuli and of ET-RB in proximal tubuli. CONCLUSIONS: The above data in human kidney allograft biopsies are consistent with an important role of the ET system in different types of renal allograft damage. This finding extends and clarifies the somewhat contradictory results in animal models.     

Cryoglobulinemic glomerulonephritis in chronic hepatitis B infection

Hepatitis B virus (HBV) infection is an uncommon cause of cryoglobulinemia. Renal cryoglobulinemia has been rarely reported in the setting of chronic hepatitis B infection. We describe a case of chronic hepatitis B infection with cryoglobulinemic glomerulonephritis (Gn) and provide information about the treatment and the evolution over a 30-month follow-up. A 41-year-old woman with chronic hepatitis B infection developed nephrotic syndrome and acute renal failure; other investigations revealed type 2 cryoglobulinemia; HBV DNA was detected in the cryoprecipitate. Renal biopsy showed findings of cryoglobulinemic Gn. She was given lamivudine, corticosteroids, plasma exchange, and mycophenolate mofetil. The renal function improved, nephrotic syndrome remitted, and HBV DNA became undetectable; there was no compromise of the liver function.