Victoriano Pardo

Glomerular Lesions in the Acquired Immunodeficiency Syndrome

Between January 1982 and December 1983, 75 patients with the acquired immunodeficiency syndrome were identified in our hospitals: 35% used intravenous drugs, 50% had proteinuria in excess of 0.5 g/dL, and 10% were nephrotic. Glomerular changes seen at autopsy in 36 patients included frequent mesangial lesions and deposits associated with mild asymptomatic proteinuria. Focal and segmental glomerular sclerosis was found in 5 patients and 4 of these had the nephrotic syndrome. Whereas reversible episodes of acute renal failure were not uncommon, terminal episodes of acute renal insufficiency occurred in 14 patients. The short survival of these patients may prevent the development of chronic renal failure.

Renal Disease in Children with the Acquired Immunodeficiency Syndrome

Abstract Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (±SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27±19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38±31 months. Although none of them went on to have renal failure, four died within 8±7 months. Ten of the 12 patients with proteinuria died during ...

The Clinical Spectrum of Renal Disease Associated With Human Immunodeficiency Virus

A nephrology consultation was called on 100 adult patients of 1,635 (6.1%) patients with human immunodeficiency virus (HIV) infection seen between 1982 and 1987 at the University of Miami/Jackson Memorial Medical Center. Renal disease was observed in all groups of patients with a risk factor for HIV infection with a lesser incidence, however, among homosexuals. Intravenous drug (IVD) use and possibly race appear to be important factors in the development of renal complications. Renal disease was the dominant clinical feature in eight asymptomatic HIV carriers and in 34 patients with AIDS-related complex (ARC) who had not developed the opportunistic infections and/or malignancies associated with acquired immunodeficiency syndrome (AIDS). Ninety-one percent of consultations were requested for evaluation of proteinuria and/or renal failure. Nephrotic range proteinuria, in excess of 3 g/24 h, was present in 52 patients, and was less prevalent in homosexuals than in other groups at risk. Renal failure (serum creatinine greater than or equal to 5 mg/dL), initially present in 32 patients, eventually developed in 69 and improved in only 18 of them. A renal biopsy, obtained for work-up of nephrotic syndrome (22 patients) or renal insufficiency (3 patients), uncovered a picture of focal and segmental glomerulosclerosis in all 25 instances. Overall, 76 patients are dead, seven are lost to follow-up, and 17 are alive, of whom eight (four HIV carriers, two patients with ARC, and two with AIDS) are on maintenance hemodialysis with a mean survival time of 217 days.

Factors associated with poor outcomes in patients with lupus nephritis.

The objective of this study was to identify the factors associated with important clinical outcomes in a case-control study of 213 patients with lupus nephritis. Included were 47% Hispanics, 44% African Americans and 9% Caucasians with a mean age of 28 years. Fifty-four (25%) patients reached the primary composite outcome of doubling serum creatinine, end-stage renal disease or death during a mean follow-up of 37 months. Thirty-four percent African Americans, 20% Hispanics and 10% Caucasians reached the primary composite outcome (P < 0.05). Patients reaching the composite outcome had predominantly proliferative lupus nephritis (WHO classes: 30% III, 32% IV, 18% V and 5% II, P < 0.025) with higher activity index score (7 ± 6 versus 5 ± 5, P<0.05), chronicity index (CI) score (4 ± 3 versus 2 ± 2 unit, P<0.025), higher baseline mean arterial pressure (MAP) (111 ± 21 versus 102 ± 14 mmHg, P<0.025) and serum creatinine (1.9 ± 1.3 versus 1.3 ± 1.0 mg/dL, P<0.025), but lower baseline hematocrit (29 ± 6 versus 31 + 5%, P<0.025) and complement C3 (54 ± 26 versus 65 + 33 mg/dL, P<0.025) compared to controls. More patients reaching the composite outcome had nephrotic range proteinuria compared to controls (74% versus 56%, P<0.025). By multivariate analysis, CI (hazard ratio [95% CI] 1.18 [1.07-1.30] per point), MAP (HR 1.02 [1.00-1.03] per mmHg), and baseline serum creatinine (HR 1.26 [1.04-1.54] per mg/dL) were independently associated with the composite outcome. We concluded that hypertension and elevated serum creatinine at the time of the kidney biopsy as well as a high CI are associated with an increased the risk for chronic renal failure or death in patients with lupus nephritis.

Review: Lupus nephritis: pathologic features, epidemiology and a guide to therapeutic decisions

Systemic lupus erythematosus may present with renal manifestations that frequently are difficult to categorize and lupus nephritis is an important predictor of poor outcome. The type and spectrum of renal injury may remain undiagnosed until full-blown nephritic and/or nephrotic syndrome appear with increased risk of end-stage renal disease. These abnormalities occur within the first few years after the diagnosis of lupus is made on clinical grounds and with the support of laboratory tests in high risk patients. An early renal biopsy is helpful in patients with an abnormal urinalysis and/or reduced glomerular filtration rate and the results form the basis for therapeutic decisions. The biopsy also provides vital prognostic information based on histological categorization of different types of lupus nephritis, the degree of activity, chronicity and the immunopathogenesis. In the current armamentarium, the use of cyclophosphamide and azathioprine and recently mycophenolate mofetil, reduce morbidity and maintenance therapies reduce the risk of end-stage renal disease. Clinical trials underway promise new, effective and safe immunosuppressive regimens for the treatment of proliferative lupus nephritis.

Nephropathy associated with sickle cell anemia: An autologous immune complex nephritis: II. Clinicopathologic study of seven patients☆

A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.

Nephropathy associated with sickle cell anemia: An autologous immune complex nephritis: I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis☆

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patients kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

Benign primary hematuria: Clinicopathologic study of 65 patients

Abstract Renal biopsy specimens were examined in a group of 65 patients with primary hematuria who met the following criteria: urine protein excretion under 1 g in 24 hours or a negative Albustix ® in a concentrated specimen, absence of hypertension and normal renal function. The median age at discovery of the disease was 13 years, and the median duration of the hematuria at biopsy was two years. Recurrent gross hematuria was present in 38 instances. Thirty of the 65 renal biopsy specimens showed mesangial proliferative glomerulonephritis and in 44 there were red blood cells in the tubules. Mesangial deposits of a variety of immunoglobulins and/or third component of complement (C3) were identified in 30 of the 44 biopsy specimens examined. Immunoglobulin M (IgM) was the predominant immunoglobulin. Electron dense mesangial deposits were identified only in 12 cases; however, ultrastructural study of the biopsy specimens led to the detection of one patient who was probably suffering from Alports syndrome. There was a poor correlation between histologic lesions and immunohistochemical findings. Thirty-nine patients were followed for a median period of four years without evidence of any deterioration of renal or any other manifestation of renal or systemic disease, although half of these patients still showed bleeding in the last urinalysis. Thus, the name benign primary hematuria appears appropriate to designate this clinical syndrome. The use of pathologic terms such as focal glomerulonephritis or immunoglobulin A (IgA) nephropathy (Bergers disease) has been a cause of ambiguity since there is not a consistent correlation between these lesions and clinical manifestations. Because the discrete mesangial changes may be predicted virtually from the clinical presentation, kidney biopsy may not seem to be indicated in the majority of these patients unless there is an increase in urinary protein excretion or other manifestations of renal, genitourinary or systemic disease appear.

Lupus nephritis: A clinical review for practicing nephrologists

The renal manifestations in systemic lupus erythematosus (SLE) are protean and difficult to categorize into clinical syndromes and histologic classes. Lupus nephritis is frequently unrecognized until full-blown nephritic and/or nephrotic syndrome with renal failure emerge. Epidemiologically, approximately one third of SLE patients from unselected populations have renal involvement early during the disease. Most renal abnormalities emerge within the first few years of SLE diagnosis. Currently, most nephrologists agree that an early renal biopsy is worthwhile in those SLE patients with abnormal urinalysis and/or reduced renal function. First, it provides a histologic categorization of the glomerulonephritis as well as an assessment of the degree of activity and chronicity. Second, it provides vital prognostic information. Third, it is beneficial in planning a more rational therapy with or without potentially toxic immunosuppressive agents. Over the last 3 decades, many controlled clinical trials for treatment of lupus nephritis have been completed with a few therapeutic immunosuppressive regimens. Among those agents used. cyclophosphamide and azathioprine provide a reduction of morbidity in those patients afflicted with proliferative forms of lupus glomerulonephritis. A new immunosuppressive agent, mycophenolate mofetil, is being studied for treatment of proliferative forms of lupus glomerulonephritis in a controlled clinical trial at our institution. Immunosuppressive agents and the availability of dialysis and transplantation have improved the survival of patients with lupus nephritis, in particular those with proliferative forms.

Pigmented nodules (black adenomas) of the adrenal: An autopsy study of incidence, morphology, and function

Abstract Both adrenal glands from 100 consecutive autopsies were sectioned at 3 mm. intervals and examined grossly and microscopically for pigmented nodules. These were present in 37 patients. Pigmented nodules are brown to black lesions, discernible with the naked eye, which typically arise at the corticomedullary junction and grow into the cortex. Occasionally they extend through the medulla. They are not encapsulated and are usually sharply circumscribed grossly; histologically, they often display drifting of pigmented cells into adjacent tissue. The histochemical characteristics and electron microscopic appearance of the pigment are typical of lipofuscin. The clinical records of the 37 patients with pigmented nodules did not reveal any higher incidence of hypertension or electrolyte or endocrine disturbance than those of a control group consisting of the remaining 63 patients of this series. We also studied the clinical records of 104 patients with pigmented nodules found in random adrenal sections in 1000 consecutive autopsies. The adrenal pigmented nodule is apparently nonfunctioning. No association of this lesion with a clinical picture of endocrine disturbance, electrolyte imbalance, or hypertension could be established.