Renal Disease

September 26, 2011

Renal (kidney) disease is a significant health care problem. As of 2000 (the most recent data available from the U.S. Renal Data Service report), the federal government’s cost of providing renal replacement therapy to patients with end-stage renal disease (ESRD) was over 12 billion dollars. Over the past decade, the increase in ESRD program costs has outpaced that of the general Medicare program by approximately 50% and presently accounts for 5.8% of the Medicare program. This is up from 4.5% over the past decade. Most of the increase is due to an increase in the patient population that has nearly doubled to 260,000 people. It is estimated that 20 million people have some form of renal disease in the United States, many of whom will progress to ESRD. Within the ESRD program, women are disproportionately represented in the Medicaid and Medicare populations.

MANIFESTATIONS OF RENAL DISEASE

As with hypertension, most people with renal disease are initially asymptomatic (without symptoms). Screening urinalysis or blood work are the most common ways with which renal disease is initially detected. Screening urinalysis in children or young adults as part of camp or school health examination may reveal hematuria (blood in urine) or proteinuria (protein in urine). Adults, as part of an insurance examination or routine annual examination, may show, in addition to hematuria or proteinuria, evidence of renal insufficiency by an elevation of the serum blood urea nitrogen (BUN) or creatinine (both BUN and creatinine are naturally occurring substances in the blood). An abnormal urinalysis is noted when there are more than 3-5 red blood cells (rbc) per high-powered field (hpf) on a microscope-viewed slide, or the detection of protein on the dipstick dipped in a urine sample. In order to measure the amount of protein, a 24-hour urine collection or spot urine (one-time urine collection sample) for protein and creatinine will need to be obtained. To screen for abnormal proteins, a urine protein electrophoresis and immunoelectrophoresis (specialized procedures that stratify/categorize urine proteins) may need to be performed.

Renal involvement can reflect prerenal causes, postrenal causes, or intrinsic (renal tissue) disease. Pre-renal causes most commonly reflect abnormalities in renal blood flow (from congestive heart failure, volume depletion, or cirrhosis of the liver) that become manifest (or more pronounced) if someone is also ingesting certain medications such as anti-inflammatory drugs. Generally speaking, there is a disproportionate rise in the BUN compared to the creatinine (>15-20:1 ratio). The urinalysis (both dipstick and microscopic) is typically normal. Hypertension may also be a reflection of renal hypoperfusion (low blood flow) even in the absence of abnormalities in renal function studies. The presence of hypertension in a woman in her late teens and early 20s, or the presence of marked hypertension in a woman without a family history of hypertension raises the possibility of fibromuscular dysplasia (narrowing of arteries due to thickening of artery wall lining).

Postrenal causes typically manifest as hydronephrosis (dilated kidney) or hydroureter (dilated ureter—tube from the kidney to the urinary bladder). Acquired causes of urinary tract obstruction (UTO) include intrinsic and extrinsic processes. Intrinsic causes include direct disease of the kidney and/or related disorders such as kidney stones, blood clots, impaired bladder function (neurogenic bladder) in diabetes mel-litus, ureteral or urethral strictures, and tumors of the renal pelvis, ureter, or bladder. Extrinsic processes include reproductive tract causes such as pregnancy, fibroids, endometriosis, cancer of the cervix or ovaries, kidneys, or ureter or bladder. Depending on the etiology, the urinalysis may be abnormal, for example, hematuria with stones or tumors.

PATIENTS WITH HEMATURIA AND PROTEINURIA

In order to understand the patient’s condition, the physician will need an appropriate medical history and must conduct a physical examination. If there is isolated hematuria, the physician must evaluate whether it is renal (in the kidney) or nonrenal (related structures such as the bladder or ureter). Renal causes may manifest with abnormal changes in rbcs when the red cells are viewed under a microscope. These abnormalities include rbc casts (abnormal clumping of blood cells), rbcs that have “buds” or “nipples,” or rbcs that are fragmented. If these changes are not present or predominant, then the physician must conduct a urologic evaluation. In cases where it is suspected that the patient has intrinsic disease, the patient is generally evaluated initially with an ultrasound. However, radio-logic imaging of patients with suspected postrenal causes is generally performed with a CT scan of the abdomen and pelvis. If the evaluation points to a renal cause, then additional laboratory testing may be in order (e.g., blood testing for autoimmune disease such as lupus, or for inflammation of the blood vessel walls known as vasculitis) along with a consideration of a renal biopsy (removal of a small piece of kidney tissue for microscopic inspection).

The detection of isolated proteinuria almost invariably reflects a renal cause. Protein excretion is measured and based upon the clinical setting, a protein electrophoresis and immunoelectrophoresis may be performed. Additional blood testing may be obtained. After the initial evaluation, a renal biopsy may be in order. The detection of hematuria and proteinuria most often reflects a renal cause and would be evaluated as described above.

If renal insufficiency is present, then it is necessary to determine whether it reflects an acute (short term) or chronic (long term) process. A renal ultrasound is usually

more accurate than a CT scan to determine size. Small kidneys reflect chronicity. If the clinical picture is suggestive of an acute process, then a renal biopsy is generally in order. Abnormal laboratory values for BUN and creatinine only first appear after the loss of at least 50% of renal function. Therefore, early in the course of renal failure, the BUN and creatinine are not sensitive markers. In addition, since creatinine is a reflection of muscle mass, small-framed individuals and women will have normal creatinine values at the lower limits of the normal range.

RENAL DISEASE IN WOMEN

Although most renal disorders occur with nearly equal frequency in males and females, there are certain diseases more likely to occur in women. The two most common are lupus nephropathy (LN) and analgesic nephropathy (AN).

Systemic lupus erythematosus (SLE) occurs 13 times more frequently in females than males and is more common and severe in blacks. It afflicts young individuals especially in the third and fourth decades. Lupus neph-ropathy is typically more severe in children and in blacks. Although the cause is unknown, there is a role for genetic and hormonal factors. At the time of diagnosis of SLE, an abnormal urinalysis or renal insufficiency is already present in approximately 50% of patients. Over time approximately 75% of patients will manifest renal involvement with renal insufficiency present in about 30%. Generally speaking, specific therapy using immuno-suppressants (medications to treat abnormal autoimmune system functioning) is considered when severe protein-uria and/or severe renal insufficiency are present. Given the complexities of the decision-making process, therapy is coordinated by a nephrologist (a doctor who specializes in the kidneys) and/or a rheumatologist. The renal prognosis has improved significantly over the past few decades.

Analgesic nephropathy occurs 5-7 times more frequently in women. It is more commonly diagnosed in the southeastern United States. Chronic headaches, joint pain, and other chronic pain syndromes are the most common reasons for consuming analgesics. The development of AN requires long-term ingestion of combination analgesics (e.g., aspirin, acetaminophen, caffeine). Epidemiologic studies have noted the regular ingestion of at least six tablets daily for more than 3 years. At the time of diagnosis, patients usually have nocturia (need to urinate during times the individual should be sleeping at night), sterile pyuria (white blood cells in the urine), anemia, and hypertension. Stopping consumption of combination analgesics is necessary.

PREGNANCY AND THE KIDNEY

Normal pregnancy results in changes in renal function. These changes are important to appreciate in the evaluation of women who are being seen for possible renal disease. By the end of the first trimester, the glomerular filtration rate (amount of urine processed/ filtered by the kidney) increases by approximately 50%. The blood pressure decreases substantially over the first 28 weeks of pregnancy and increases slightly thereafter till delivery.

PREGNANCY AND RENAL DISEASE

Pregnancy in women with renal disease can affect the natural history of the underlying disorder, and renal disease can affect the maternal and fetal outcomes. Effect of pregnancy on renal disease generally depends upon the severity of the underlying renal disease and the presence of hypertension at the time of conception. Overall, proteinuria increases in nearly 50% of women and hypertension worsens in nearly 25% of women. With normal renal function or mild renal insufficiency, less than 10% of women will manifest a permanent decline in renal function. When the creatinine is more than mildly elevated, the risk of worsening renal insufficiency has been shown to increase by approximately 40%. Due to amenorrhea (lack of menstruation) or anovulatory menstrual cycles (menstruation without ovulation), the ability to conceive when the creatinine is very elevated (more than 3 mg/dl) and carry the fetus to term is generally very low.

Pregnancy in women with diabetes and SLE is not uncommon. In the diabetic patient without underlying nephropathy, pregnancy does not appear to increase the subsequent development of diabetic nephropathy (kidney damage due to diabetes). As with other forms of renal disease, renal insufficiency (creatinine > 1.5 mg/dl) at the time of conception has been associated with irreversible deterioration of renal function. In one study, about 45% of patients were affected.

Effect of renal disease on pregnancy is a reflection of the severity of renal insufficiency. Mild renal insufficiency is associated with an increase in preterm labor

(approximately 20%), stillbirth (approximately 5%), and small for gestational age (SGA) infants (approximately 24%). Superimposed preeclampsia (pregnancy-associated disorder with abnormal blood pressure) occurs in about 10% of patients. In moderate and severe renal insufficiency, preterm labor, perinatal mortality, and other complications are more common. Uncontrolled hypertension (mean arterial pressure > 105 mm Hg at conception) has been estimated to be associated with a 10-fold increase in relative risk of fetal death.

In women with diabetic nephropathy, both perinatal morbidity and mortality have improved markedly in association with excellent blood sugar control. As in the nondiabetic patient with renal disease, the risk of complications of pregnancy, including preeclampsia, is increased with worsening renal insufficiency.

In women with SLE and preexisting LN, predictors of adverse fetal outcome include proteinuria (approximately 60% fetal loss), presence of abnormal blood (antiphospholipid), antibodies (approximately 75% fetal loss), and hypertension (approximately 30% fetal loss). Due to the small number of patients studied with renal insufficiency at the outset of pregnancy, the role of renal insufficiency on fetal outcome is presently unclear. In patients with SLE and LN (irrespective as to whether LN preceded pregnancy or first occurred during pregnancy), overall fetal loss has improved over the past three decades. Between 1990 and 2000, fetal loss occurred in 30% of pregnancies.

GENERAL APPROACH TO THERAPY

Specific treatment strategies for the multiple etiologies (causes) of renal disorders are beyond the scope of this text. There is a common therapeutic approach to patients with renal disease. This approach involves: (a) excellent blood pressure control (blood pressures ~120/80 mmHg); (b) the use of specific medications such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB); (c) control of elevated blood fats/lipid (hyperlipidemia) with diet, exercise, and statin drugs; (d) restriction of dietary salt intake; (e) avoidance of excess protein intake; (f) control of elevated blood phosphorus concentrations with diet and use of medications that serve as phosphate binders; (g) control of metabolic acidosis (excessive accumulation of blood acid) with sodium bicarbonate.

Since an elevation in the serum creatinine to values just above the upper limits of normal generally reflects a loss of at least 50% of renal function, a referral to a nephrologist at this time is recommended.

See Also: Autoimmune disorders, Cardiovascular disease, Diabetes, Hypertension, Pregnancy, Systemic lupus erythematosus

Suggested Reading

  • Appel, G. B., Radhakrishnan, J., & D’Agat, V. (2000). Secondary glomerular disease. In B. M. Brenner (Ed.), Brenner and Rector’s the kidney (pp. 1350-1448). Philadelphia, PA: W. B. Saunders.
  • Berger, B. E. (2003). Interstitial renal disease. In D. E. Hricik, R. T. Miller, & J. R. Sedor (Eds.), Nephrology secrets (pp. 136-139). Philadelphia: Hanley & Belfus.
  • Falk, R. J., Jennette, J. C., & Nachman, P. H. (2000). Primary glomerular disease. In B. M. Brenner (Ed.), Brenner and Rector’s the kidney (pp. 1263-1349). Philadelphia: W. B. Saunders.
  • Hou, S. (1999). Pregnancy in chronic renal insufficiency and end-stage renal disease. American Journal of Kidney Disease, 33, 235-252.
  • Jungers, P., & Chauveau, D. (1997). Pregnancy in renal disease. Kidney International, 52, 871-885.
  • Mackie, A. D. R., Doddridge, M. C., Gamsu, H. R., et al. (1996). Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and nephropathy with moderate renal impairment. Diabetic Medicine, 13, 90-96.
  • Moroni, G., Quaglini, S., Banfi, G., et al. (2002). Pregnancy in lupus nephritis. American Journal of Kidney Disease, 40, 713-720.
  • Sanders, C. L., & Lucas, M. J. (2001). Medical complications of pregnancy. Obstetrics and Gynecology Clinics, 28, 593-600.
  • United States Renal Data System (USRDS). (2002). Annual data report: Atlas of end-stage renal disease in the United States (National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases). Bethesda, MD.

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