Proteinuria and renal insufficiency three years after treatment of gastric lymphoma.
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Aged↗
Biomedical subjects
G S Markowitz
Publications and source records attributed to G S Markowitz.
Three-year-old boy with partial Fanconi syndrome.
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Basement Membrane↗
Renal manifestations of concurrent systemic lupus erythematosus and HIV infection.
Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection, yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen concurrently in the same patient. Many of the cases of combined HIV infection and SLE reported in the literature are patients with SLE before HIV infection and who did not undergo renal biopsy at a time when both processes were present. We report the clinical manifestations and renal biopsy findings in four subjects with concurrent HIV infection and SLE and compare them with the seven previously reported cases in the literature. Taken together, most patients were black (91%) and male (73%), and approximately half (55%) were children with perinatal HIV infection. These demographics differ markedly from those of idiopathic SLE, a disease that predominantly affects female adults. Renal presentations included proteinuria and hypocomplementemia, frequently with hematuria and renal insufficiency. Renal biopsy findings in 10 cases included all classes of lupus nephritis (class IIb in two cases, class III in one case, class IV in three cases, class V in three cases, class III and V in one case), two of which also displayed overlapping features of HIV-associated nephropathy (HIVAN). One case had isolated findings of HIVAN. This cohort provides a unique population in which to study interacting pathomechanisms between HIV infection and SLE.
Acute Kidney Injury↗
Heavy chain deposition disease: the disease spectrum.
A 45-year-old white woman was found to have microscopic hematuria during her annual physical examination. After a negative urologic workup, she returned 5 months later with nephrotic syndrome, renal insufficiency, and hypocomplementemia. Renal biopsy showed a nodular sclerosing glomerulopathy that could not be further characterized because of inadequate tissue for immunofluorescence. The patient returned 8 months later with chronic renal failure. A repeat renal biopsy showed deposits composed of immunoglobulin G (IgG) heavy chain and complement components C3 and C1 along glomerular, tubular, and vascular basement membranes, with negativity for kappa and lambda light chains, findings consistent with heavy chain deposition disease (HCDD). The heavy chain subclass was exclusively IgG3. Staining with monoclonal antibodies to epitopes of the constant domains of IgG heavy chain showed a CH1 deletion, indicating a truncated heavy chain. On review of the previously reported cases of HCDD, common clinical presentations include nephrotic syndrome, renal insufficiency, hematuria, and, in some cases, hypocomplementemia. In most patients, the hematologic disorder is mild, without overt myeloma. Light microscopy shows a nodular sclerosing glomerulopathy, and heavy chain deposits are detectable within basement membranes throughout the kidney by immunofluorescence and electron microscopy. There is no effective treatment for this condition, and virtually all patients progress to chronic renal failure.
Complement System Proteins↗
Polycystin-2 expression is developmentally regulated.
PKD2 encodes a protein of unknown function that is mutated in 15% of autosomal dominant polycystic kidney disease (ADPKD) families. We used polyclonal antisera against PKD2 to examine the pattern of Pkd2 expression in staged mouse embryos. Staining for Pkd2 was documented as early as the 6th embryonic day (day E6) in the embryonic ectoderm and endoderm. Low-intensity staining is seen in metanephric ureteric bud at day E12.5. By day E15.5, the adult pattern of expression is established with low level staining in proximal tubules and high level, basolateral staining in distal tubules. Pkd2 expression is first detected in the medullary collecting ducts at postnatal day 14. Outside of the kidney, Pkd2 expression is widely distributed in utero and more restricted postnatally. The greatest intensity of staining is seen in the fetal but not adult adrenal cortex and in red blood cell precursors. Expression also is seen in multiple endocrine organs, in cardiac, skeletal, and smooth muscle, and in multiple mesenchymal tissues. The diffuse distribution and early expression of Pkd2 suggest a fundamental developmental role. The persistent strong expression in adult kidney is consistent with a more organ-specific function in the maintenance of the mature metanephric tubule.
Animals↗
Hepatitis C virus-associated glomerular disease in patients with human immunodeficiency virus coinfection.
Chronic infection with hepatitis C virus (HCV) has been linked to the development of glomerular disease. HCV infection is highly prevalent among intravenous drug users, a population that is also at risk for HIV coinfection. This study reports the clinical-pathologic features and outcome of HCV-associated glomerular disease (HCV-GD) in 14 patients with HIV coinfection. All were intravenous drug users and all but one were African-Americans. Renal presentations included renal insufficiency, microscopic hematuria with active urine sediment, hypertension, and nephrotic syndrome or nephrotic-range proteinuria without hypercholesterolemia. Hypocomplementemia and cryoglobulinemia were present in 46 and 33% of patients, respectively. The predominant renal biopsy findings were membranoproliferative glomerulonephritis type 1 or type 3 (Burkholder subtype) in 79% of patients and membranous glomerulopathy with atypical features in 21% (including overlap with collapsing glomerulopathy in one patient). The clinical course was characterized by rapid progression to renal failure requiring dialysis. The overall morbidity and mortality were high with median time of 5.8 mo to dialysis or death. Although most patients died in renal failure, cause of death was primarily attributable to long-term immunosuppression and advanced AIDS. Patients with AIDS had shorter survival than those without (median survival time of 6.1 mo versus 45.9 mo, log-rank test P = 0.02). Only two patients were alive with stable renal function at follow-up of 28.5 mo. In patients with HCV-GD, coinfection with HIV leads to an aggressive form of renal disease that can be easily confused with HIV-associated nephropathy. Although hypocomplementemia, cryoglobulinemia, and more prominent hypertension and microscopic hematuria may provide clues to the presence of HCV-GD, renal biopsy is essential to differentiate HCV-GD from HIV-associated nephropathy.
AIDS-Associated Nephropathy↗
Immunoreactivity for LN2 and LN3 distinguishes small cell carcinomas from non-small cell carcinomas in the lung.
Immunoreactivity to LN2 and LN3, monoclonal antibodies that recognize components of the class II major histocompatibility complex, was assessed in 72 cases of non-small cell lung carcinoma (NSCLC) (32 biopsy specimens, 40 resection specimens) and 64 cases of small cell carcinoma (56 biopsy specimens, 8 resections) of the lung. All cases were reviewed independently by three pathologists for histological classification. Only 1 of the 64 small cell carcinomas showed immunoreactivity for LN2, and none of the 64 cases showed reactivity for LN3. Among the non-small cell carcinomas, 25 of 48 cases were positive for LN2 and 43 of 71 were positive for LN3; the sensitivity was greater for adenocarcinoma (78.5%) than for squamous cell carcinoma (37%). A combined sensitivity of 64.7% was observed when the results of LN2 and LN3 were combined, and this sensitivity was not significantly diminished in the biopsy subset of cases (59.4%). Differentiation within histological subtypes of NSCLC (ie, well, moderate, or poorly differentiated) did not alter test sensitivity. In conclusion, LN2 and LN3, used alone or in combination, appear highly specific for non-small cell carcinoma and moderately sensitive in both biopsy and resection specimens; therefore, these antibodies may be diagnostically useful in distinguishing small cell from non-small cell carcinoma of the lung.
Antibodies, Monoclonal↗
Splenic para-amyloid material: a possible vasculopathy of the acquired immunodeficiency syndrome.
We have observed perivascular para-amyloid in the spleens of acquired immune deficiency syndrome (AIDS) patients at autopsy. Whether this phenomenon is unique to AIDS patients or is a common degenerative phenomenon in the spleen has not been determined. Autopsy spleens from 355 patients (171 AIDS, 184 non-AIDS) were graded for presence of splenic para-amyloid material (SPAM) on a scale of 0 to 3. The average ages of the AIDS and non-AIDS groups were 38.4 and 60.4 years, respectively. All SPAM-positive AIDS cases had age-matched non-AIDS controls. Selected positive cases were examined ultrastructurally. Of the 171 AIDS patients, 55 had SPAM; in 30 cases, it was considered grade 2 or 3. Although none of the non-AIDS cases were graded 2 or 3, eight of them were grade 1. SPAM is highly correlated with AIDS (32.1 v 4.3%; P < .0001), with a specificity of 95.6% and a positive predictive value of 87.3%. These perivascular deposits correspond to areas of periarteriolar lymphoid sheaths and appear to be in continuity with arteriolar adventitia. Ultrastructurally, they contain collagen, long-spaced collagen, fibrillin, and occasional residual cells. No viral particles were noted. SPAM appears to be more prevalent and in greater quantity in AIDS patients. It does not correlate with advanced age; it can be mistaken for amyloid. Its consistent association with the adventitia of vessels raises the possibility of a new vasculopathy of AIDS; it also may be related to follicular involution and hyalinization associated with regression of prior follicular hyperplasia.
AIDS-Related Opportunistic Infections↗
Polyclonal immunoglobulin G deposition disease: a unique entity.
We report a unique case of tubular polyclonal immunoglobulin G (IgG) deposition disease (PIDD) superimposed on diabetic nephropathy in an 84-year-old man presenting with subacute renal failure and proteinuria. The deposits were located exclusively between the tubular epithelial cells and the tubular basement membranes (TBMs) and stained intensely with antisera to IgG heavy chain and both kappa and lambda light chains. Electron microscopy revealed large predominantly extracellular electron-dense deposits with a distinctive curvilinear substructure. The associated light microscopic findings of tubular simplification with features of acute tubular necrosis implicate this tubulopathy as the cause of the acute renal failure. This appears to represent a unique entity that does not fit into any previously described category of renal tubular immune complex or immunoglobulin deposition disease.
Aged↗
De novo minimal change disease.
Beyond the acute posttransplantation period, glomerular causes of proteinuria in the renal allograft include recurrent glomerulopathy, transplant-associated entities, and de novo disease. We present a case of de novo minimal change disease with reversible acute renal failure occurring 2.5 years posttransplantation in a 56-year-old man. The cause of end-stage renal disease in the native kidney was membranous glomerulopathy. De novo minimal change disease in the renal allograft is an extremely rare entity requiring stringent clinical-pathological criteria for diagnosis. Many of the cases previously reported as de novo minimal change disease fail to meet these criteria. We review the eight reported cases that appear to fulfill a strict definition of minimal change disease in the context of the current report.
Acute Kidney Injury↗
Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy.
The most common form of glomerular disease seen in association with hepatitis C virus (HCV) infection is membranoproliferative glomerulonephritis, with or without associated cryoglobulinemia. This study examines four cases of fibrillary glomerulonephritis and two cases of immunotactoid glomerulopathy in association with HCV infection. Findings at presentation included proteinuria, renal insufficiency, and hematuria. Renal biopsy revealed a membranoproliferative pattern of glomerular disease in five cases, and a membranous glomerulopathy with mesangial proliferative features in one. On immunofluorescence, all cases stained with IgG and C3. Electron microscopy revealed fibrils of the expected diameter, 16 to 28 nm in fibrillary glomerulonephritis and 33 to 45 nm in immunotactoid glomerulopathy. In only one case were cryoglobulins detected (at low titer and on only one of three assays). Antiviral therapy was not given in any of the six cases. Outcomes were mixed, with progression to renal failure occurring in two patients and persistent proteinuria with stable or improved renal function in three. Follow-up is not available on the sixth case. Both fibrillary glomerulonephritis and immunotactoid glomerulopathy have features that overlap with cryoglobulinemic glomerulonephritis. The relatedness of these three entities in a subset of patients with HCV infection suggests a common pathogenic mechanism of glomerular deposition of organized deposits.
Adult↗
Acute interstitial nephritis following treatment with anorectic agents phentermine and phendimetrazine.
A 47-year-old mildly obese female began a weight reduction program that included anorectic therapy with phentermine and phendimetrazine. A normal urinalysis and serum creatinine were documented at the start of therapy. After three weeks of treatment, the patient felt ill and discontinued her treatment. Subsequently she was found to have leukocyturia, a rash on her face and chest, and a rise in her serum creatinine from 0.8 mg/dl to 2.1 mg/dl. A renal biopsy confirmed the diagnosis of acute interstitial nephritis. The patient was treated with corticosteroids and her renal function returned to normal. Despite the recent withdrawal of two anorectic agents due to data linking them to severe cardiac and pulmonary disease, the appetite suppressants phentermine and phendimetrazine remain in widespread usage for the treatment of obesity. This case represents the first report of acute interstitial nephritis associated with phentermine or phendimetrazine.
Acute Disease↗
An evaluation of the effectiveness of oral iron therapy in hemodialysis patients receiving recombinant human erythropoietin.
Iron balance is critical for adequate erythropoiesis in hemodialysis patients treated with recombinant human erythropoietin (EPO). The role of oral iron therapy in maintaining or replenishing iron stores has not yet been well defined in such patients. We undertook a double-blind, placebo-controlled study to evaluate the efficacy of oral iron in 49 hemodialysis patients, divided into two groups, based on adequate or deficient iron stores. These groups were treated for 3 months with 150 mg elemental iron (Polysaccharide complex, Central Pharmaceuticals) or placebo, twice daily. Laboratory parameters were followed for five months. These parameters included: hematocrit (Hct), ferritin, transferrin saturation (Tsat), and zinc protoporphyrin (ZPP). A side-effects questionnaire was recorded monthly. Our results indicate that iron replete patients show evidence of falling iron stores during the study period; this observation was identical in both oral iron and placebo subgroups. Iron deficient patients had a significantly greater drop-out rate due to side effects when compared to iron replete patients (33% vs. 8%), despite equivalent responses to the side-effect questionnaire. We conclude: 1) Oral iron fails to maintain iron stores in iron replete patients; 2) Iron deficiency observed in this study may be due to poor medication compliance rather than side-effects.
Administration, Oral↗
Autopsy patterns of disease among subgroups of an inner-city Bronx AIDS population.
The Bronx, New York, has a large, inner-city, AIDS population which contains a greater proportion of women and intravenous drug users and a lower percentage of homosexuals than the U.S. AIDS population overall. Because this population is reflective of the evolving trends in the national AIDS population, our objective was to gain an understanding of patterns of infections, malignancies, and cause of death among these individuals. All autopsies (252) performed on patients with AIDS at two hospitals affiliated with a major academic center in the Bronx between 1982 and 1995 were reviewed. Cytomegalovirus (CMV) as an infection or as a cause of death (COD) occurred more commonly among patients who had been infected with HIV through sexual relations (p = 0.0002 and p = 0.0011, respectively). Bacterial pneumonia was the most common source of pulmonary infection, although Pneumocystis carinii pneumonia was more often a cause of death. A higher frequency of aspergillus infection in female subjects was also noted (p = 0.010). These and other observations may have ramifications for treatment and prevention in analogous AIDS inner-city populations.
Acquired Immunodeficiency Syndrome↗
Comparison of changing autopsy trends in the Bronx population with acquired immunodeficiency syndrome.
The opportunistic infections, malignancies, and causes of death related to acquired immunodeficiency syndrome (AIDS) are changing, perhaps as a result of improved treatment, prophylaxis, and education. With its high percentage of persons who acquired the human immunodeficiency virus from intravenous drug (IVD) use, the population of patients with AIDS in the Bronx is potentially unique. All of the 257 consecutive adult human immunodeficiency virus and/or AIDS cases from two Bronx teaching hospitals from 1982 through 1995 were collected. The reports were reviewed for patient demographics, opportunistic infections, malignancies, and causes of death. One hundred thirteen cases from 1982 through 1988 were compared with 144 cases from 1989 through 1995, separated by the institution of antiretroviral therapy and Pneumocystis carinii (PCP) prophylaxis in the latter period. Male homosexuality as a risk factor significantly decreased from 24.8% of the cases in our study from the 1982/88 period to 12.5% during the 1989/95 period (P = 0.014), but IVD use cases showed no change. Cases of AIDS in heterosexual patients increased from 23.9 to 36.1% (P = 0.041) but did not achieve statistical significance unless the unknown risk category (a population shown to be infected predominantly through heterosexual transmission) was included. The prevalence of PCP at autopsy as an opportunistic infection decreased from 37.2 to 25% (P = 0.04), and its prevalence as a cause of death decreased from 31.9 to 13.9% (P = 0.007). This decrease was seen in the homosexual and heterosexual populations but not in the population of IVD users. The homosexual population, as opposed to the population of IVD users, may have taken greater advantage of PCP treatment and prevention. As a result, bronchopneumonia, not PCP, is now the leading cause of death among the patients with AIDS in this study. These findings have important implications for therapy and prophylaxis to control the spread of AIDS and its related infections, particularly in an inner city population troubled by drug use and poverty.
AIDS-Related Opportunistic Infections↗
Renal vein thrombosis treated with thrombolytic therapy: case report and brief review.
Renal vein thrombosis (RVT) can occur as a complication of the nephrotic syndrome. We present the case of a young woman with systemic lupus erythematosus with nephrotic syndrome and bilateral RVT with extension of the thrombus into the vena cava to the level of the right atrium and multiple pulmonary emboli. She was treated acutely with streptokinase, with complete resolution of the thrombi. In general, anticoagulation is the mainstay of therapy for RVT. Review of the literature reveals that thrombolytic therapy can be used safely and appears to have been reserved for those patients with the most severe disease or the more grave prognosis. we feel that thrombolytic therapy is warranted in the presence of bilateral RVT with acute renal failure, massive clot size with high risk of acute embolic events, or recurrent pulmonary emboli, in the absence of overriding contraindications.
Adolescent↗
Membranous glomerulopathy associated with graft-versus-host disease following allogeneic stem cell transplantation. Report of 2 cases and review of the literature.
We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG.
Acute Disease↗