AZOTEMIA AND TYPICAL URINALYSIS FOR DIABETIC NEPHROPATHY

AZOTEMIA
Azotemia is an elevation of blood urea nitrogen (BUN) and serum creatinine levels. The reference range for BUN is 8-20 mg/dL, and the normal range for serum creatinine is 0.7-1.4 mg/dL. Urine formation by each nephron involves 3 main processes, as follows: Filtration at the glomerular level Selective reabsorption from the filtrate passing along the renal tubules Secretion by the cells of the tubules into this filtrate Perturbation of any of these processes impairs the kidneys excretory function, resulting in azotemia Epidemiology The most frequent causes were ATN (45%); prerenal (21%); acute or chronic renal failure, mostly due to ATN and prerenal disease (13%); urinary tract obstruction (10%); glomerulonephritis or vasculitis (4%); acute interstitial nephritis (2%); and atheroemboli (1%). Etiologies of CKD differ around the world. Diabetic nephropathy as a cause of CKD is on the rise in developed and developing countries Etiology Prerenal Azotemia Occurs as a consequence of: Impaired renal blood flow or decreased perfusion resulting from decreased blood volume Decreased cardiac output (congestive heart failure) Decreased systemic vascular resistance Decreased effective arterial volume from sepsis or hepatorenal syndrome, or renal artery abnormalities. May be superimposed on a background of chronic renal failure. Iatrogenic factors, such as excessive diuresis and treatment with ACE inhibitors Intrarenal Azotemia Occurs as a consequence of: Injury to the glomeruli, tubules, interstitium, or small vessels. It may be acute oliguric, acute nonoliguric, or chronic Systemic disease, nocturia, proteinuria, loss of urinary concentrating ability (low urine specific gravity), anemia, and hypocalcemia Postrenal Azotemia Occurs as a consequence of obstruction of urine flow: In bilateral ureteral obstruction from tumors or stones Retroperitoneal fibrosis Neurogenic bladder Bladder neck obstruction from prostatic hypertrophy or carcinoma and posterior urethral valves It may be superimposed on a background of chronic renal failure Pathophysiology There are 3 pathophysiologic states of Azotemia Prerenal Azotemia Prerenal azotemia refers to elevatoions in BUN and creatinine levels resulting from problems in the systemic circulation that decrease flow to the kidneys. In prerenal azotemia, decreased renal flow stimulates salt and water retention to restore volume and pressure. When volume or pressure is decreased, the baroreceptor reflexes located in the aortic arch and carotid sinuses are activated. This leads to sympathetic nerve activation, resulting in renal afferent arteriolar vasoconstriction and renin secretion through 1 receptors. A decrease in volume or pressure is a nonosmotic stimulus for hypothalamic production of antidiuretic hormone, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as BUN, creatinine, calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (< 20 mEq/L). Intrarenal Azotemia Intrarenal azotemia, also known as acute renal failure (ARF), renal-renal azotemia, and acute kidney injury (AKI), refers to elevations in BUN and creatinine resulting from problems in the kidney itself. The most common causes of nonoliguric AKI are acute tubular necrosis (ATN), aminoglycoside nephrotoxicity, lithium toxicity, and cisplatin nephrotoxicity. The pathophysiology of acute oliguric or nonoliguric AKI depends on the anatomic location of the injury: In ATN, epithelial damage leads to functional decline in the ability of the tubules to reabsorb salt, water, and other electrolytes. Excretion of acid and potassium is also impaired. In more severe ATN, the tubular lumen is filled with epithelial casts, causing intraluminal obstruction and resulting in a declining GFR

Acute interstitial nephritis is characterized by inflammation and edema, which result in azotemia, hematuria, sterile pyuria, white blood cell (WBC) casts with variable eosinophiluria, proteinuria, and hyaline casts Glomerular diseases may reduce GFR by changing basement membrane permeability and stimulating the reninaldosterone axis. Such diseases are often manifested as nephrotic or nephric syndrome. In nephrotic syndrome, the urinary sediment is inactive, and there is gross proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema. Azotemia and hypertension are uncommon initially, but their presence may indicate advanced disease Some patients with nephrotic syndrome may present with ARF. Impairment of capillary circulation in the kidney due to edema (nephrosarca) and tubular obstruction from protein casts, as well as decreased effective circulating volume, have been proposed as potential mechanisms for the development of ARF in patients with nephrotic syndrome. In nephritic syndrome, the urinary sediment is active with WBC or RBC casts, granular casts, and azotemia. Proteinuria is less obvious, but increased salt and water retention in glomerulonephritis can lead to hypertension, edema formation, decreased output, low urinary excretion of sodium, and increased specific gravity Etc.

Postrenal Azotemia Postrenal azotemia refers to elevations in BUN and creatinine levels resulting from obstruction in the collecting system. Obstruction to flow leads to reversal of the Starling forces responsible for glomerular filtration. Progressive bilateral obstruction causes hydronephrosis with an increase in the Bowman capsular hydrostatic pressure and tubular blockage that leads to progressive decline in and ultimate cessation of glomerular filtration, azotemia, acidosis, fluid overload, and hyperkalemia Unilateral obstruction rarely causes azotemia. There is evidence that if complete ureteral obstruction is relieved within 48 hours of onset, relatively complete recovery of GFR can be achieved within a week; little or no further recovery occurs after 12 weeks. Complete or prolonged partial obstruction can lead to tubular atrophy and irreversible renal fibrosis. Hydronephrosis may be absent if obstruction is mild or acute or if the collecting system is encased by retroperitoneal tumor or fibrosis.

Diagnosis HISTORY TAKING Patients with prerenal azotemia commonly have a history of diarrhea, vomiting, profound heat exhaustion, excessive sweat loss, concurrent illness that impairs their ability to eat and drink adequately, hemorrhage, liver disease, congestive heart failure, and polyuria (eg, caused by lithium intoxication, diuretics, diabetes, or diabetes insipidus) Patients with intrarenal azotemia may have a history of nocturia, polyuria, proteinuria, shock, and edema. There may be a personal or family history of congenital or systemic diseases, especially diabetes, hypertension, systemic lupus erythematosus (SLE), other collagen vascular diseases, hepatitis B (HBV), hepatitis C (HCV), syphilis, multiple myeloma, and AIDS Obtain a detailed medication history, looking for nephrotoxic medications (especially antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], angiotensin-converting enzyme [ACE] inhibitors, diuretics, and herbal remedies), chemical exposure, and intravenous (IV) drug abuse (associated with exposure to HIV, HBV, and HCV infections) Patients with postrenal azotemia frequently have a history of renal colic, dysuria, frequency, hesitancy, urgency incontinence, pelvic malignancy or irradiation, or benign prostatic hypertrophy PHYSICAL EXAMINATION In suspected prerenal azotemia, look for tachycardia; orthostatic hypotension (systolic blood pressure drop greater than 20 mm Hg or diastolic drop greater than 10 mm Hg from supine to standing); hypotension; signs of dehydration, including dry mucous membranes, loss of skin turgor, and loss of axillary sweat; and signs of congestive heart failure or hepatic insufficiency. In suspected intrarenal azotemia, look for hypertension and its end-organ effects, such as hypertensive retinopathy and left ventricular hypertrophy (apical impulse displaced lateral to midclavicular line), rash, joint swelling or tenderness, needle tracks, hearing abnormality, palpable kidneys, abdominal bruits, pericardial rub, and asterixis Postrenal azotemia (obstruction) is suggested by a palpable bladder that is dull to percussion and the presence of a rectal or pelvic mass on digital examination LABORATORY STUDIES Diagnostic indices are commonly used to differentiate prerenal azotemia from intrarenal or postrenal azotemia. Picture below the treatment Treatment The goals of therapy are to increase renal perfusion and to maintain urine output. Drugs used in the management of patients with azotemia include diuretics, adrenergic agents, plasma volume expanders, and corticosteroids. Diuretics Used to induce urine output in acute tubular necrosis (ATN) and to treat edema and hypertension. They increase urine excretion by inhibiting sodium and chloride reabsorption at different sites in the nephron. Ex: Furosemide, Hydrochlorothiazide, Chlorothiazide, Metolazone Volume Expanders Increase plasma oncotic pressure and mobilize fluid from the interstitial space into the intravascular space in hypoalbuminemic patients. They enhance delivery of furosemide to distal tubule. Ex: Albumin

Corticosteroids The potent anti-inflammatory agents and immunosuppressants. They suppress humoral and cellular response to tissue injury, thereby reducing inflammation. Ex: Prednisone, Prednisolone, Methylprednisolone Alpha/Beta Adrenergic Agonists Adrenergic agents stimulate vasodilation of the renal vasculature and enhance perfusion Ex: Dopamine

Diagnostic Studies

Management Prerenal Azotemia If volume depletion is due to free water loss, the serum sodium is often elevated by 10 mEq/L from baseline. The fluid to be administered should consist of hypotonic solutions such as 0.5% saline or 5% dextrose in water (D5W). Alert patients should be encouraged to drink as much free water as they can tolerate; otherwise, free water can be administered via a nasogastric tube Decreased cardiac output requires optimization of cardiac performance through careful use of diuretics, an angiotensinconverting enzyme (ACE) inhibitor, beta blockers, nitrates, positive inotropic agents (including dobutamine), and, when indicated, specific therapy for the cause of impaired cardiac function Adequate nutrition and effective treatment of sepsis may improve oncotic pressure and normalize vascular permeability, thereby decreasing the systemic shunting Intrarenal Azotemia Acute Renal Failure (Acute Kidney Injury) For ischemic or nephrotoxic acute tubular necrosis (ATN) due to shock (hypovolemic, cardiogenic, septic), the initial approach is to restore volume and pressure (with fluid replacement and vasopressors, respectively) and to withdraw any nephrotoxic drugs.[7] . If the patient becomes oliguric or anuric from shock, volume in the form of crystalloids should be aggressively administered as boluses (eg, 300 mL every 2 hours, rather than 150 mL every hour) Chronic Kidney Disease It is important that patients with chronic kidney disease (CKD) be referred early to a nephrologist for the management of complications and for the transition to renal replacement therapy (ie, hemodialysis, peritoneal dialysis, and renal transplantation). Prognosis The prognosis of ARF/AKI generally is poor and depends on the severity of the underlying disease and the number of failed organs. Whereas mortality in patients with simple ARF/AKI without other underlying disease is 7-23%, that in ICU patients on mechanical ventilation is as high as 80%. The prognosis of CKD depends on the etiology. Patients with diabetic kidney disease, hypertensive nephrosclerosis, and ischemic nephropathy (ie, large-vessel arterial occlusive disease) tend to have progressive azotemia resulting in ESRD. Different types of glomerulonephritis have major differences in prognosis: some are quite benign and rarely progress to ESRD, whereas others progress to ESRD within months. About 50% of patients with polycystic kidney disease progress to ESRD by the fifth or sixth decade of life

TYPICAL URINALYSIS FOR DIABETIC NEPHROPHATY

A 24-hour urinalysis for urea, creatinine, and protein is extremely useful in quantifying protein losses and estimating the glomerular filtration rate (GFR). Typically, the urinalysis results from a patient with established diabetic nephropathy show proteinuria varying from 150 mg/dL to greater than 300 mg/dL, glucosuria, and occasional hyaline casts. Microalbuminuria is defined as albumin excretion of more than 20 g/min, or albumin -to-creatinine ratio (g/g) > 30. This phase indicates incipient diabetic nephropathy and calls for aggressive management, at which stage the disease may be potentially reversible (ie, microalbuminuria can regress).

In general, onset of overt proteinuria with less than 5 years of the onset of diabetes, an active urine sediment with dysmorphic red cells and casts, or an abrupt decline in kidney function suggest a nondiabetic etiology of the kidney disease