Nephrotic syndrome from hypercalcemia in a patient with primary hyperparathyroidism.

The nephrotic syndrome developed in a 47-year-old woman in association with severe hypercalcemia (23.5 mg/dl) from primary hyperparathyroidism. Other causes for hypercalcemia were sought and were not found. The nephrotic syndrome remitted spontaneously within two weeks of normalization of the serum calcium level. Kidney biopsy specimens showed deposition of electron-dense material, thought to be calcium, in the glomerular basement membranes initially and in the mesangium as well six months later.

Immune complex nephropathy in mixed connective tissue disease.

Initial reports on the clinical spectrum of mixed connective tissue disease (MCTD) indicated that renal involvement was uncommon. Four of 20 patients with MCTD underwent renal biopsy and all showed evidence of immune complex trapping with a membranous glomerulonephritis in three patients. Clinically evident renal disease was absent in two patients. These findings suggest that renal involvement in MCTD may be more prevalent than previously indicated.

Neuropsychiatric problems in mixed connective tissue disease.

A group of 20 patients with mixed connective tissue disease, followed for up to five years, was found to have a 55 per cent incidence of neuropsychiatric problems. An aseptic meningitis-like syndrome was the most common presentation and was rapidly responsive to corticosteroid therapy. Other findings were psychosis, convulsions, peripheral neuropathy, trigeminal neuropathy and cerebellar ataxia. An abnormal cerebrospinal fluid was found in five patients; mild pleocytosis, an increased protein content and a first phase colloidal gold curve were the main abnormalities. These neuropsychiatric problems have not been a cause of mortality in this group of patients with mixed connective tissue disease.

Nondiabetic renal disease in patients with diabetes mellitus.

Renal diseases other than diabetic nephropathy were found in 10 of 122 diabetic patients who underwent renal biopsy between 1960 and 1982. These diseases included lupus glomerulonephritis, acute post-streptococcal glomerulonephritis, membranoproliferative glomerulonephritis (type I), focal glomerulosclerosis, idiopathic membranous nephropathy, and nonspecific immune complex glomerulonephritides. Because some of these disorders can alter the management and prognosis of renal disease in diabetic patients, the appearance of urinary abnormalities or deterioration in renal function inconsistent with the natural history of diabetic nephropathy raises the possibility of a nondiabetic renal disease and should lead to a more detailed evaluation.

Course of renal pathology in patients with systemic lupus erythematosus.

Evaluation of the course of lupus nephropathy by serial kidney biopsy in 50 patients revealed a complex pattern of transitions from one histologic class to another. A high rate of transformations (56 percent) was observed, with fewer than half the patients remaining in the original category. Although the general trend was towards transformation to a less severe lesion (WHO classes III and IV transforming into classes II and V), this was certainly not the rule for all individual classes. These transformations were rarely predictable on the basis of available clinical, laboratory, or pathologic information, and were less common in younger patients. These results help clarify the pathologic behavior of lupus nephropathy in the modern therapeutic era and highlight the value of pathologic examination for the planning and evaluation of therapy in selected patients.

Glomerulonephritis associated with male pseudohermaphroditism and nephroblastoma.

A child with male pseudohermaphroditism, Wilms' tumor, and glomerulonephritis (Drash syndrome) was found to have a proliferative glomerular lesion, extensive renal cortical interstitial and glomerular scarring, and marked renal tubular foam cell change. By electron microscopy, dense deposits were seen in mesangial areas with focal extension into the subendothelial space. Segmental deposits of immunoglobulin and complement were found in the glomeruli by immunofluorescence microscopy. A consistent karyotypic abnormality consisting of isochromosomes of the long arms of 1 and 17, and an interstitial deletion of the long arm of 5 was found in cultures of tumor cells, but no karyotypic abnormalities were found in peripheral blood lymphocytes or non-neoplastic kidney. Renal failure in this case has progressed despite the surgical removal of the tumor. These findings are similar to those reported previously in patients with this syndrome and suggest a common pathophysiological abnormality in all of the patients reported so far.

Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases.

Acute renal insufficiency is a common problem, yet one that is frequently reversible with proper diagnosis and treatment. Although it has been argued that a renal biopsy is not needed for diagnosis in most cases of acute renal failure in the elderly, other studies have shown frequent disagreements between clinical and renal biopsy diagnoses in such cases. To investigate the causes of acute renal insufficiency in patients aged at least 60 years who underwent a renal biopsy and possible correlations between biopsy findings and renal survival, we first identified all native renal biopsy specimens from patients aged 60 years or older processed at The University of Chicago Medical Center (Chicago, IL) from 1991 through 1998 and reviewed the clinical records to determine the indication for the biopsy. We then reviewed again the records of those patients who underwent biopsy because of acute renal insufficiency, recorded the primary renal biopsy diagnosis in each of these cases, and obtained follow-up information for patients who underwent biopsy before July 1996. During the study period, 1,065 of 4,264 biopsy specimens (25.0%) received were obtained from patients aged 60 years or older, and acute renal insufficiency was the indication for biopsy in 259 of these patients (24.3%). The most frequent primary diagnoses on these latter biopsy specimens were pauci-immune crescentic glomerulonephritis (GN) with or without arteritis, 31.2% of biopsy specimens; acute interstitial nephritis, 18.6%; acute tubular necrosis (ATN) with nephrotic syndrome, 7.5%; atheroemboli, 7.1%; ATN alone, 6.7%; light chain cast nephropathy (LCCN), 5.9%; postinfectious GN, 5.5%; anti-glomerular basement membrane antibody nephritis, 4.0%; and immunoglobulin A (IgA) nephropathy and/or Henoch-Schönlein nephritis, 3.6%. Eight biopsy specimens (3.2%) showed only benign nephrosclerosis without an apparent cause of acute renal insufficiency, and another six specimens were inadequate. The renal biopsy diagnosis was in agreement with the prebiopsy clinical diagnosis (or differential diagnosis) in 107 of the 161 cases (67%) in which such information was provided. The distribution of diagnoses was similar in patients in the age groups of 60 to 69, 70 to 79, and 80 years or older, although younger age correlated significantly with improved renal and patient survival. The relative risk for progression to end-stage renal disease (ESRD) also increased according to diagnostic categories: LCCN (greatest risk) > GN other than pauci-immune > atheroemboli congruent with pauci-immune crescentic GN > tubulointerstitial diseases other than LCCN (the latter category including ATN with nephrotic syndrome). Development of ESRD correlated significantly with decreased patient survival. In summary, renal biopsy in patients aged 60 years or older with acute renal insufficiency uncovered the cause in greater than 90% of the cases and provided clinically useful information with respect to expectation for renal survival and potential treatment options.

Practical use of electron microscopy for the diagnosis of glomerular disease.

In the past few years many clinically significant new glomerular lesions have been reported from observations made on renal biopsy specimens by electron microscopy. The clinical applicability of electron microscopy is illustrated by examples of specific ultrastructural patterns of glomerular reaction making possible a more accurate diagnosis, prognosis, and prediction of the response to treatment.

The differential diagnosis of crescentic glomerulonephritis. The pathology of specific lesions with prognostic implications.

Combined findings from light and electron microscopy with immunofluorescence studies make a definitive diagnosis possible in most cases of crescentic glomerulonephritis. The patient's prognosis and pattern of response to therapy are matters of immediate concern in the light of recent developments in nephrology. The frequency of crescentic lesions varies depending on the specific types of disease, but the idiopathic lesion is seldom seen.

IgA nephropathy: morphologic predictors of progressive renal disease.

IgA nephropathy has a variable course and leads to renal failure in a substantial number of cases. In an attempt to identify prognostic indicators in this disease, we evaluated the clinical and pathologic findings of 20 unselected patients with IgA nephropathy, 13 of whom were followed for 1.5 to 5 years (mean 2.8 years). Biopsy specimens were obtained from all patients and were examined by light and electron microscopy and by immunofluorescence. The activity and severity of the lesions were graded according to a modified classification used by Meadow et al. for the nephropathy associated with Henoch-Schönlein purpura. The results reveal a correlation between the histopathologic grading in the initial biopsy and the clinical outcome: Patients with mild (grade II) or moderate (grade III) lesions had a benign course or showed evidence of active disease without deterioration of renal function, whereas all patients with grade IV or V lesions who were followed for more than one year developed end-stage renal failure. These observations suggest that histologic grading at initial renal biopsy may be a useful prognostic indicator of the clinical outcome of IgA nephropathy.

Immune complex glomerulonephritis and amyloidosis in Schistosoma japonicum infected rabbits.

Epidemiologically, the incidence of renal pathology in patients with chronic parasitic infections is higher than expected. In particular, schistosomiasis may have an association with renal failure. 24 New Zealand White rabbits were, therefore infected with 250 or 500 Schistosoma japonicum cercariae of the Philippine-Leyte strain and studied for eight months to determine if rabbits with long-term infections were suitable hosts for the study of schistosomal nephropathy. Clinical evidence for renal disease consisted of proteinuria, haematuria, and casts. Of the 18 surviving infected animals, six had trace amounts of protein in their urine, three had significant proteinuria ranging from 100 to 300 mg%, four exhibited haematuria and 14 were positive for the presence of proteinaceous cast formation. The clinical findings correlated with the histological data. Periodic open renal biopsies on a subgroup of the animals revealed no changes until about the sixth month. At eight months after infection, five (28%) of the 18 rabbits had amyloid deposits and 15 (83%) had some degree of renal change which included mild focal, diffuse intracapillary, and crescentic glomerulonephritis with mesangial and subendothelial complex trapping. Periodic-acid Schiff staining graphically demonstrated wire loops and tubular casts. Immunofluorescence showed that 15 (83%) of the infected animals exhibited diffuse mesangial and peripheral capillary wall deposition of IgG while 14 contained IgM (78%). The third component of complement was found in only five (28%) of the infected rabbits. Parasite antigen could not be detected in the glomeruli of any of the animals. Kidneys from age-matched controls were within normal limits. Electron microscopy of glomeruli from several animals demonstrated the presence of subendothelial and mesangial immune complex deposition similar to that seen in systemic lupus erythematosus. These findings show that schistosomiasis japonica in the rabbit offers an excellent model system for studying not only the renal pathology associated with human schistosomiasis but also the pathogenesis of amyloidosis which is a frequent sequela observed in a variety of chronic inflammatory infections.

Efficacy of percutaneous renal biopsy in obese patients under computerized tomographic guidance.

The performance of percutaneous renal biopsy under ultrasound guidance in markedly obese patients is associated with technical difficulties because of the production of poor image quality. Fluoroscopy can be potentially used as an alternative guidance method when the kidneys are not visualized sonographically. However, the presence of uremia in an obese patient imposes an additional risk when fluoroscopy is used because of possible nephrotoxicity from the use of radiocontrast dye. Computerized tomography (CT) provides advantages over these two methods because of the production of excellent spatial resolution of images leading to accurate localization of the kidneys. We performed 59 consecutive percutaneous renal biopsies in 58 patients using CT as guidance. The body mass index (BMI) defined as weight in kilograms/(height in meter)2 [Watson et al. 1979], was used to assess the severity of obesity. Twenty-nine patients had Grade 0 (BMI less than or equal to 24.9), 17 had Grade I (BMI 25-29.9), 7 had Grade II (BMI 30-39.9) and 5 had Grade III (BMI greater than or equal to 40) obesity. Thirty-two patients had superimposed uremia of varying degrees. Image quality was maintained in all four groups, and tissues adequate for diagnosis were obtained in 98% of the attempts. Complications were minimal with no deaths, nephrectomies or surgical interventions attributable directly to the biopsy procedure itself. We recommend the use of CT guidance in the grossly obese patients (Grade II or III) when their kidneys are poorly visualized by sonography.

Changing histopathology patterns in lupus nephropathy.

The initial clinical and histologic renal findings and the subsequent course of 90 patients with SLE were evaluated in a study of the natural history of lupus nephropathy. Initial renal biopsy revealed focal glomerulonephritis in 32 patients, diffuse glomerulonephritis in 47, membranous nephropathy in seven and minimal changes in four. Forty-one patients were rebiopsied three months to five years later; ten of 15 patients with focal glomerulonephritis showed progression to diffuse glomerulonephritis or membranous nephropathy, whereas changes in morphologic pattern were less common in the other types of lupus nephropathy. There was no difference between the patients with the focal lesion who progressed and those who did not in age, sex distribution, duration of SLE prior to biopsy, renal function, and serological studies; however, the patients with progression initially had more proteinuria, higher histologic activity on light microscopy, and more intensive glomerular electron-dense deposition. Focal lupus glomerulonephritis progresses frequently to diffuse glomerular involvement. Certain clinical and morphologic findings at initial evaluation may help to predict future progression in the course of lupus nephropathy.

Reversible renal failure from isolated granulomatous renal sarcoidosis.

A patient presented with a 6 month history of progessive renal failure. Serum creatinine was 7.1 mg/100 ml, creatinine clearance 4 ml/minute and hematocrit 22%. Skin tests for tuberculosis, trichophyton, SK/SD and candida were all unreactive and all cultures were negative or showed normal growth. A renal biopsy revealed non-caseating epithelial granulomas and foreign body multinucleated giant cells. No deposits or micro-organisms were seen on electron microscopy. Bone marrow and lymph node biopsies were unremarkable and no lung pathology was present. Therapy with systemic prednisone produced a dramatic improvement with serum creatinine diminishing to 1.3 mg/100 ml, creatinine clearance increasing to 81 ml/minute and hematocrit improving to 39%. A search of the literature has failed to reveal similar reports of reversible renal failure from isolated granulomatous renal sarcoidosis.

Renal biopsy in pregnancy-induced hypertension.

Percutaneous renal biopsy, introduced 20 years ago, has revolutionized our understanding of many diseases affecting the kidney. In studies performed in nonpregnant subjects substantial progress in defining the mechanism, prognosis and treatment of a host of renal diseases was achieved by correlating clinical findings and renal function with light, electron and immunofluorescent microscopy. In the early 1960's investigators described the renal lesions associated with preeclampsia and made initial clinicopathological correlations, but relatively few studies combining light, electron and immunofluorescent findings in pregnant women have appeared to date. This is because clinical circumstances rarely justify even the minimal risks of biopsy during gestation, and after the disease has regressed, nephrology consultation is not requested in the puerperium. In addition, a report of excessive bleeding and other complications in gravidas, although not encountered by other groups (and personal experience of the authors), has contributed to the lack of enthusiasm for renal biopsy on obstetrical services and to the belief that this procedure is not advisable both during gestation and the immediate puerperium. This article reviews the renal morphology of preeclampsia and described those aspects of it in which current knowledge is still incomplete. Indications, benefits, and risks of kidney biopsy during pregnancy or puerperium will be discussed, with emphasis on the prognostic information to be expected from the procedure which may help in predicting the outcome of future pregnancies.