Overview of heavy proteinuria and the nephrotic syndrome
- Ellie Kelepouris, MD, FAHA
Ellie Kelepouris, MD, FAHA
- Professor of Medicine
- Chief, Division of Nephrology and Hypertension
- Drexel University College of Medicine
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
INTRODUCTION AND TERMINOLOGY
Diseases of the glomerulus can result in three different urinary and clinical patterns: focal nephritic; diffuse nephritic; and nephrotic. (See "Differential diagnosis and evaluation of glomerular disease".)
●Mild nephritic – Disorders resulting in a mild nephritic sediment are generally associated with inflammatory lesions in less than one-half of glomeruli on light microscopy (focal glomerulonephritis). The urinalysis reveals red cells (which often have a dysmorphic appearance), occasionally red cell casts, and mild proteinuria (usually less than 1.5 g/day). The findings of more advanced disease are usually absent, such as heavy proteinuria, edema, hypertension, and renal insufficiency. These patients often present with asymptomatic hematuria and proteinuria discovered on routine examination or, occasionally, with episodes of gross hematuria.
●Severe nephritic – The urinalysis in diffuse glomerulonephritis is similar to focal disease, but heavy proteinuria (which may be in the nephrotic range), edema, hypertension, and/or renal insufficiency may be observed. Diffuse glomerulonephritis affects most or all of the glomeruli.
●Nephrotic – The nephrotic sediment is associated with heavy proteinuria and lipiduria, but few cells or casts. The term "nephrotic syndrome" refers to a distinct constellation of clinical and laboratory features of renal disease. It is specifically defined by the presence of heavy proteinuria (protein excretion greater than 3.5 g/24 hours), hypoalbuminemia (less than 3 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease are also frequently observed.
Isolated heavy proteinuria without edema or other features of the nephrotic syndrome is suggestive of a glomerulopathy (with the same etiologies as the nephrotic syndrome), but is not necessarily associated with the multiple clinical and management problems characteristic of the nephrotic syndrome. This is an important clinical distinction because heavy proteinuria in patients without edema or hypoalbuminemia is more likely to be due to secondary focal segmental glomerulosclerosis (FSGS) (due, for example, to diabetes) .
- Praga M, Borstein B, Andres A, et al. Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition. Am J Kidney Dis 1991; 17:330.
- Rivera F, López-Gómez JM, Pérez-García R, Spanish Registry of Glomerulonephritis. Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004; 66:898.
- Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997; 30:621.
- Braden GL, Mulhern JG, O'Shea MH, et al. Changing incidence of glomerular diseases in adults. Am J Kidney Dis 2000; 35:878.
- Simon P, Ramee MP, Boulahrouz R, et al. Epidemiologic data of primary glomerular diseases in western France. Kidney Int 2004; 66:905.
- Malafronte P, Mastroianni-Kirsztajn G, Betônico GN, et al. Paulista Registry of glomerulonephritis: 5-year data report. Nephrol Dial Transplant 2006; 21:3098.
- Bahiense-Oliveira M, Saldanha LB, Mota EL, et al. Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing? Clin Nephrol 2004; 61:90.
- Gesualdo L, Di Palma AM, Morrone LF, et al. The Italian experience of the national registry of renal biopsies. Kidney Int 2004; 66:890.
- Heaf J. The Danish Renal Biopsy Register. Kidney Int 2004; 66:895.
- Swaminathan S, Leung N, Lager DJ, et al. Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol 2006; 1:483.
- D'Agati V. The many masks of focal segmental glomerulosclerosis. Kidney Int 1994; 46:1223.
- Hausmann R, Kuppe C, Egger H, et al. Electrical forces determine glomerular permeability. J Am Soc Nephrol 2010; 21:2053.
- Reiser J, von Gersdorff G, Loos M, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest 2004; 113:1390.
- Schönenberger E, Ehrich JH, Haller H, Schiffer M. The podocyte as a direct target of immunosuppressive agents. Nephrol Dial Transplant 2011; 26:18.
- Gbadegesin R, Lavin P, Foreman J, Winn M. Pathogenesis and therapy of focal segmental glomerulosclerosis: an update. Pediatr Nephrol 2011; 26:1001.
- Kaysen GA, Gambertoglio J, Jimenez I, et al. Effect of dietary protein intake on albumin homeostasis in nephrotic patients. Kidney Int 1986; 29:572.
- Kaysen GA, Kirkpatrick WG, Couser WG. Albumin homeostasis in the nephrotic rat: nutritional considerations. Am J Physiol 1984; 247:F192.
- Sun X, Martin V, Weiss RH, Kaysen GA. Selective transcriptional augmentation of hepatic gene expression in the rat with Heymann nephritis. Am J Physiol 1993; 264:F441.
- Pietrangelo A, Panduro A, Chowdhury JR, Shafritz DA. Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat. J Clin Invest 1992; 89:1755.
- Sun X, Kaysen GA. Albumin and transferrin synthesis are increased in H4 cells by serum from analbuminemic or nephrotic rats. Kidney Int 1994; 45:1381.
- Moshage HJ, Janssen JA, Franssen JH, et al. Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. J Clin Invest 1987; 79:1635.
- Zacchia M, Trepiccione F, Morelli F, et al. Nephrotic syndrome: new concepts in the pathophysiology of sodium retention. J Nephrol 2008; 21:836.
- Crew RJ, Radhakrishnan J, Appel G. Complications of the nephrotic syndrome and their treatment. Clin Nephrol 2004; 62:245.
- Chen T, Lv Y, Lin F, Zhu J. Acute kidney injury in adult idiopathic nephrotic syndrome. Ren Fail 2011; 33:144.
- Vaziri ND, Kaupke CJ, Barton CH, Gonzales E. Plasma concentration and urinary excretion of erythropoietin in adult nephrotic syndrome. Am J Med 1992; 92:35.
- Vaziri ND. Endocrinological consequences of the nephrotic syndrome. Am J Nephrol 1993; 13:360.
- Mähr N, Neyer U, Prischl F, et al. Proteinuria and hemoglobin levels in patients with primary glomerular disease. Am J Kidney Dis 2005; 46:424.
- Ginsberg JM, Chang BS, Matarese RA, Garella S. Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 1983; 309:1543.
- Howard AD, Moore J Jr, Gouge SF, et al. Routine serologic tests in the differential diagnosis of the adult nephrotic syndrome. Am J Kidney Dis 1990; 15:24.
- INTRODUCTION AND TERMINOLOGY
- Minimal change disease
- Focal segmental glomerulosclerosis
- - Diagnostic issues
- Membranous nephropathy
- Hyperlipidemia and lipiduria
- Protein malnutrition
- Acute kidney injury
- Serologic studies
- Renal biopsy
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS