Elsevier

Human Pathology

Volume 43, Issue 1, January 2012, Pages 81-88
Human Pathology

Original contribution
Acquired glomerular lesions in patients with Down syndrome

https://doi.org/10.1016/j.humpath.2011.04.009Get rights and content

Summary

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.

Introduction

Down syndrome (DS) is the most common chromosome abnormality among liveborn infants. The long-term survival of persons with DS has dramatically increased over the past 50 years, largely because of improvement in medical care [1], [2]. Recent data indicate that the prevalence of DS is increasing likely because of the prolonged survival and increased maternal age, which outweigh the effect of antenatal diagnosis with subsequent pregnancy termination [3], [4]. Patients with DS have an increased risk of congenital heart disease (particularly atrioventricular septal defect and ventricular septal defect), gastrointestinal tract anomalies, autoimmune disorders (particularly hypothyroidism, celiac disease and diabetes), hematologic disorders (especially polycythemia and leukemia), hearing loss, eye problems, obesity, immune deficiency, and urinary tract anomalies (including anterior urethral obstruction, hypospadias, cystic dysplastic kidney, renal hypoplasia, and hydronephrosis) [5], [6].

Recent data suggest that glomerular disease in patients with DS is not as rare as previously thought. In a recent cross-sectional study from Spain of 69 patients with DS, aged 1 to 24 years, who were followed up in a pediatric genetics unit, 8 were found to have incidental renal disease, including chronic renal failure in 3, mild proteinuria in 3, and microscopic hematuria in 2 [7]. Renal biopsies were not performed. The diagnosis and management of glomerular disease in patients with DS are more challenging than those in the general population because of noncompliance with investigations and treatment due to learning challenges and the frequent comorbidities. Therefore, there is a need for studies specifically addressing the clinical-pathologic characteristics, treatment, and outcome in these patients. Such studies are lacking in the literature. Herein, we conducted a detailed clinical-pathologic study of 17 patients with DS who underwent a kidney biopsy for renal dysfunction.

Section snippets

Materials and methods

We reviewed the renal pathology archives at Mayo Clinic, Rochester, MN, from 1994 to 2010, and identified 18 native kidney biopsies from 17 patients with DS and renal dysfunction. For light microscopy (LM), all cases were stained with hematoxylin and eosin, periodic acid–Schiff, Masson's trichrome, and Jones methenamine silver. Standard immunofluorescence (IF) on frozen tissue was performed in 15 biopsies with available glomeruli. In 2 biopsies, glomeruli were lacking on frozen tissue and

Clinical data of the entire cohort

The clinical characteristics of all 17 patients are summarized in Table 1. The cohort consisted of 10 males and 7 females. The mean age at biopsy was 29 years (range, 6-45 years). There were 14 adults (aged ≥16 years) and 3 children. Twelve patients were whites and 5 were African Americans. Known DS-associated congenital anomalies were present in 4 patients; 3 had congenital heart disease (patent foramen ovale in 2 and ventricular septal defect in 1) and 1 had complex congenital urologic

Discussion

This study details the clinical features, pathologic findings, and outcome of 17 mostly young adult patients with DS who underwent kidney biopsy for renal dysfunction. We identified a variety of glomerular lesions in these patients, including IgAN, FSGS, MPGN, APIGN, pauci-immune crescentic GN, MGN, and lupus nephritis. In addition to our series, there have been 11 previously reported DS patients with biopsy-proven glomerular disease [9], [10], [11], [12], [13], [14]. The glomerular disease

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