Glomerular Disease Primer : Kidney Disease

  • End-stage kidney disease
  • Glomerular disease syndromes
  • Remission of glomerular disease
  • Classification of glomerular diseases
  • Assessing progressive loss of glomerular filtration rate (GFR) Stages of chronic kidney disease (CKD)

    End-stage kidney disease

    End-stage kidney disease (ESKD) is a major health problem in the US and other developed countries. ESKD occurs when patient survival requires a treatment, either chronic dialysis or kidney transplant. In the US, approximately 100,000 people reach ESKD each year and begin dialysis or undergo kidney transplant surgery. In the US, the major causes of ESKD are diabetes, hypertension, glomerulonephritis, and cystic kidney disease (primarily polycystic kidney disease). As shown in the figure below, the rates of ESKD due to diabetes and hypertension have increased sharply over the past 20 years, but the rate of increase appears to have slowed recently

    As shown in the figure, the rates of ESKD due to diabetes and hypertension have increased sharply over the past 20 years, but the rate of increase appears to have slowed recently

    Top

    Glomerular disease syndromes

    Traditionally glomerular diseases are divided into those that present with nephritic syndrome and those that present with nephrotic syndrome. These syndromes have different presentations, as listed below, but they have an important commonality: proteinuria (an increase in the amount of protein in the urine). Normally, in adults, the kidneys excrete up to 150 mg/d (0.15 g/d) of protein. Proteinuria is a common manifestation of kidney injury, including both tubular injury and glomerular injury. Glomerular diseases interfere with the normal function of the glomerular filtration barrier and can increase protein excretion above 2 g/d. Nephrotic-range proteinuria is defined as protein excretion >3.5 g/d in adults.

    Nephritic syndrome

    • hypertension, microscopic hematuria (blood visible in urine under the microscope but not necessarily visible with the naked eye)
    • red blood cell casts in the urine
    • proteinuria (often <2 g/d in adults)

    Nephrotic syndrome

    • proteinuria >3.5 g/d in adults and >40 mg/kg in children (this will appear as 3 on urine protein dipstick)
    • edema, which is the accumulation of salt water that the kidneys have not excreted; the fluid initially accumulates in the legs (shown below, pitting edema – the skin has a sustained dimple when pressure is placed)
    • low serum albumin, the major serum protein
    • elevated serum cholesterol, which is produced by the liver in response to proteinuria
    pitting edema – the skin has a sustained dimple when pressure is placed

    Top
    • Remission of glomerular disease

      Remission is defined as the complete or partial resolution of disease manifestations, with the precise definition specific to the particular disease. Relapse means the return of disease manifestations after a remission has occurred.

      Remission in nephrotic disease

      The following definitions are consensus definitions but are not universally accept.

     


    Complete remission

    Partial remission

    Children

    Definition 1: Urine dipstick negative or trace

    Definition 2: First morning urine protein/creatinine ratio <

    First morning urine protein/creatinine ratio <2

    Adults

    24 hour urine protein <0.3 g/d

    Definition 1: 24 hour urine protein – 50% fall from baseline and <3.5 g/d

    Definition 2: 24 hour urine protein <2 g/d

    Top

    Classification of glomerular diseases

    Glomerular diseases can be classified by the injury mechanism or glomerular cell target, by the presence or absence of systemic disease, and by the appearance of nephritic syndrome or nephrotic syndrome.

    Injury Systemic or primary Nephritic syndrome Nephrotic syndrome or isolated proteinuria
    Immunologic Systemic disease • Lupus nephritis• Membranoproliferative glomerulonephritis associated with hepatitis C Membranous nephropathy associated with hepatitis B or lupus
    Immunologic Primary kidney disease • IgA nephropathy• Membranoproliferative glomerulonephritis Membranous nephropathy
    Genetic Systemic disease • Alport’s nephropathy Fabry disease
    Metabolic Systemic disease -- • Diabetic nephropathy• Amyloid
    Podocyte injury Primary kidney disease -- • Minimal change disease• Focal segmental glomerulosclerosis• Collapsing glomerulopathy

    Top

    Assessing progressive loss of glomerular filtration rate (GFR)

    Serum creatinine rises as GFR falls, since creatinine is normally excreted by glomerular filtration. The relationship between GFR and serum creatinine is not linear and so following the level of serum creatinine is not a precise way to determine how rapidly GFR is falling.

    Creatinine clearance is an approximate measure of GFR and is calculated using a formula that includes serum creatinine, urine creatinine (typically from a 24 hour urine collection) and urine volume. This is a good way to estimate GFR in patients with normal kidney function. The results can be expressed as ml/min or as ml/min/1.73 m2 (adjusted to the patients’s body surface area).

    Estimated GFR (eGFR) can be determined using a formula that includes age, race, sex and serum creatinine (the MDRD equation or Levy equation). eGFR is expressed as ml/min/1.73m2. Even when creatinine clearance is expressed as ml/min/1.73m2, it tends to be higher than eGFR.

    Importantly, however GFR is measured, the kidney has enormous functional reserve. This allows a healthy individual to donate a kidney for the purposes of renal transplantation and the serum creatinine remains within the normal range. Thus a major limitation of serum creatinine (and all the above measurements) is that it remains within the normal range until extensive kidney damage has occurred.


    Stages of chronic kidney disease (CKD)

    NKF: www.kidney.org/professionals/kdoqi  Exit disclaimer

    eGFR Stage of kidney disease
    >90 ml/min/1.73m2 Normal kidney function (early kidney disease may or may not be present)
    60-90 ml/min/1.73m2 Mild CKD
    30-59 ml/min/1.73m2 Moderate CKD
    15-29 ml/min/1.73m2 Severe CKD
    <15 ml/min/1.73m2 End-stage kidney disease

    Top

  • Page last updated: February 25, 2011

    General inquiries may be addressed to:
    Office of Communications & Public Liaison
    NIDDK, NIH
    Bldg 31, Rm 9A06
    31 Center Drive, MSC 2560
    Bethesda, MD 20892-2560
    USA
    301.496.3583

    The National Institutes of Health   Department of Health and Human Services   USA.gov is the U.S. government's official web portal to all federal, state, and local government web resources and services.  This website is certified by Health On the Net Foundation. Click to verify.