questions_Nephrology

Educational objective: Understand the mechanism of action for furosemide.

Loop diuretics reduce NaCl reabsorption by inhibiting Na-K-2Cl carrier in the luminal membrane in the thick ascending limb of the loop of Henle. The efficacy is dose-related and depends on delivery of the diuretic to the site of action. Loop diuretics are highly protein bound and are therefore delivered mostly by tubular secretion rather than by glomerular filtration.

In subjects with normal renal function diuretic effect can be seen with as little as 10 mg of furosemide given orally. Maximal effect is seen with about 40 mg given intravenously. The maximum effective dose is, however, higher in patients with heart failure, advanced cirrhosis, or renal failure. In these conditions, decreased renal perfusion (with decreased drug delivery), diminished tubular secretion (because of retention of the anions in renal failure), and enhanced activity of the rennin-angiotensin-aldosterone system (enhancing sodium retention) combine to diminish the diuretic effect.

Educational objective: Understand the etiology of struvite kidney stones.

Struvite stones are associated with urinary tract infections caused by Proteus and Klebsiella. Those stones are composed of magnesium ammonium phosphate (struvite), often in combination with calcium carbonate – apatite. Normal urine is undersaturated with ammonium phosphate, and struvite stone formation can only occur if ammonia production is increased and urinary pH is elevated (this decreases the solubility of phosphate). Both situations are present during infections by proteus or klebsiella, the urease-producing organisms. Urease breaks down urinary urea into ammonia and carbon dioxide. The ammonia combines with water; the net result is increased availability of ammonium in alkaline urine.

Educational objective: review the features of metabolic acidosis in chronic renal failure.

As the number of functioning nephrons declines in chronic renal disease, the excretion of the net acid is maintained by increase in ammonia excretion per individual nephron. When net acid secretion reaches insufficient levels the glomerular filtration is generally below 40-50 ml/min, and each remaining nephron excretes ammonia at 3-4 times the normal level. This results in net retention of hydrogen ions and development of metabolic acidosis. In addition to a fall in ammonium excretion, decreased titratable acidity (mainly phosphate) also may play a role in advanced disease.

As end-stage renal disease develops, the plasma bicarbonate concentration tends to stabilize between 12-20 meq/l; levels below 10 meq/l are unusual because of buffering of the hydrogen ions by various body buffers. The anion gap is usually (but not always) elevated due to retention of such anions as phosphate, sulfate, urate, and hippurate.

Educational objective: Review options for correction of metabolic acidosis of chronic renal failure.

There are several recent studies showing the benefit of treatment for metabolic acidosis associated with advanced renal failure (keeping plasma bicarbonate concentration over 22 meq/l results in decreased development of osteopenia and hyperparathyroid bone disease, prevention of diminished albumin synthesis and lean body mass loss caused by acidosis). Alkali therapy may also be beneficial to children with growth retardation.

If alkali is given, sodium bicarbonate in daily dose of 0.5-1 meq/kg/day is the agent of choice. Sodium citrate may be used and is rapidly metabolized into bicarbonate after absorption. However, citrate may greatly enhance absorption of aluminum from the bowel. This is important in patients taking aluminum-containing antacids to control hyperphosphatemia because it may cause aluminum intoxication. An alternative method of acidosis correction in patients on maintenance dialysis is to increase the bicarbonate content of dialysate (up to 42 meq/l). This is generally well tolerated and does not induce significant postdialysis alkalosis.

Aluminum containing antacids are used to control hyperphosphatemia, and, as already mentioned, may interfere with administration of sodium citrate.

Educational objective: Understand characteristic findings in hematuria from different parts of the urinary tract.

One of the first steps in the evaluation of a patient with hematuria is to try to distinguish between glomerular and extraglomerular bleeding. Careful evaluation of the urine may help to establish the correct diagnosis. The presence of red cell casts is virtually diagnostic of glomerulonephritis or vasculitis. Absence, of course, does not exclude glomerular disease.

Evaluation of red cell morphology also may be helpful because these cells are typically uniform and round if bleeding is extraglomerular, and dysmorphic (marked variability of the size, and change of shape) with glomerular source of bleeding.

Heavy protein excretion (above 500 mg/day) is also strongly suggestive of a glomerular lesion (hematuria alone does not cause increase in the proteinuria). Blood clots, if present, are almost indicative of extraglomerular bleeding. Urine color also may be suggestive; extraglomerular bleeding causes red to pink color while glomerular bleeding tends to give a brownish “Coca cola” color.

Educational objective: review of characteristic features of multiple myeloma.

This presentation and laboratory findings are suggestive of multiple myeloma. Median age at diagnosis is about 65 years. About two thirds of patients have bone pain at presentation. Pain is most common in the back and chest, and less frequent in the extremities. Pain is usually aggravated by movement and is usually absent during the night except with change in position. Weakness and fatigue are also common symptoms.

Pallor is the most frequent physical finding. Liver is palpable in about 20% and spleen in 5% of patients. Bone metastases are most commonly osteolytic (thought to be mediated by cytokine production) and may result in hypercalcemia (20-30% of patients). Renal failure is common and may be a presenting manifestation of multiple myeloma.

Elevated serum proteins with proteinuria (light chains) are one of the hallmarks of multiple myeloma and may result in amyloidosis.

Metastatic disease is unlikely to be associated with either hyperproteinemia or osteoarthritis, which is more widespread and tends to be located in the lower lumbar spine. Epidural abscess is usually associated with systemic signs of infection and elevated WBC.

Vertebral compressions are common in patients with multiple myeloma but those are caused by the bony destruction by masses of plasma cells rather than osteoporosis.

Educational objective: Review causes of pseudohyperkalemia.

Pseudohyperkalemia refers to elevation of the measured plasma potassium level because of the potassium movement out of cells during or after a blood specimen has been drawn. The most common cause is mechanical trauma to red blood cells during venipuncture (hemolysis). It can also occur in hereditary spherocytosis and in familial pseudohyperkalemia in which there is increased temperature-dependent leakage of potassium out of red blood cells after the specimen is collected.

Potassium also moves out of white blood cells and platelets after clotting has occurred (0.1-0.5 meq/l in normal subjects). In cases of marked leukocytosis (100,000 per mm3) and thrombocytosis (400,000 mm3) as in the cases of leukemia or myeloproliferative disease, the measured potassium may be up to 9 meq/l. For every 100,000 mm3 increases in platelets, count serum potassium rises for about 0.15 meq/l.

Pseudohyperkalemia should be suspected in all patients in whom there is no apparent reason for potassium level elevation, and in asymptomatic patients.

Educational objective: Review common causes of urinary tract infections.

Approximately 70% of all urinary tract infections are caused by E. coli. About 30% of all E. coli related urinary tract infections are resistant to ampicillin. Approximately 25% of all urinary tract infections are due to staphylococcus saprophyticus. Chlamydia species account for 20% of urinary tract infections, and other enterobacteriaceae account for the rest.

Educational objective: Review of methods for protein measurements in urine.

A 24-hour urine collection and determination of albumin in it is, of course, a gold standard for the detection of microalbuminuria. Screening, however, can be achieved more simply by measurements of the albumin in the urine samples. Positive results must be confirmed by 24-hour urine collection (to distinguish from transient causes of microalbuminuria – fever, heart failure, exercise, and poor glycemic control, etc.).

Urine specimens may be random or timely. Random urine samples suffer from the dependence of albumin concentration of the urine production at the time of the test. To minimize this affect a timely urine sample may be used, and in this case an early morning sample is most consistent in terms of volume production. However, this dependence on volume may be entirely avoided by calculation of the albumin-to-creatinine ratio in the urine specimen. A value above 30mg/g suggests albumin excretion above 30 mg/day and, thus, microalbuminuria.

The diluting segment of the nephron is the thick ascending limb of the loop of Henle. This segment actively reabsorbs NaCl without water. This process leads to urine that is hypotonic compared to the plasma and creates free water excretion.

Educational objective: Review mechanism of action of ADH.

The major renal effect of the antidiuretic hormone (ADH) is to increase the water permeability of the luminal membrane of the collecting duct epithelium. In the absence of ADH, permeability of the epithelium is very low and reabsorption of water decreases, leading to polyuria. When ADH is present, epithelial permeability increases markedly and water is reabsorbed as the collecting ducts traverse the renal medulla of ever-increasing osmolality up to a maximum of 1200 mosm/kg at the tip of the papilla. Thus, maximal ADH effect results in low urine flow and high urine osmolality. With ADH deficiency, urine flow may be as high as 15-20 mL/min and urine osmolality is less than 100 mosm/kg.

Educational objective: Review causes of neurogenic diabetes insipidus.

Causes of neurogenic diabetes mellitus:

• -Hypophysectomy, complete or partial (may be due to trauma)
• -Surgery for suprasellar tumors (about 20% in transsphenoidal approach)
• -Idiopathic
• -Familial
• -Tumors or cysts (intra- and suprasellar- craniopharyngiomas, etc.)
• -Histiocytosis
• -Granulomas (in sellar and suprasellar area)
• -Infections (in sellar and suprasellar area)
• -Interruption of blood supply
• -Autoimmune

Hypokalemia causes nephrogenic diabetes insipidus.

Educational objective: Review causes of nephrogenic diabetes insipidus.

Causes of nephrogenic diabetes insipidus

Cyclophosphamide is one of the medications that causes vasopressin release, and as such it is a cause of the syndrome of inappropriate ADH secretion.

Educational objective: Emphasize association of bronchogenic carcinoma and SIADH.

Conditions associated with syndrome of inappropriate ADH secretion (SIADH):

• -Malignant lung disease, particularly bronchogenic carcinoma
• -Nonmalignant lung disease (e.g., tuberculosis, pneumonias)
• -Tumors at other sites (especially lymphoma, sarcoma)
• -Central nervous system trauma and infections
• -Drugs that stimulate vasopressin release – clofibrate, chlorpropamide, thiazides, carbamazepine, phenothiazines, vincristine, cyclophosphamide, opiates
• -Endocrine disease – adrenal insufficiency, myxedema, anterior pituitary insufficiency

Nephrogenic diabetes insipidus is not a cause of hyponatremia. The rest of the options may cause hyponatremia but in different clinical conditions.

Educational objective: Review therapy for SIADH.

The treatment of SIADH depends upon the underlying cause. A patient with a drug-induced disorder should be treated by withholding the drug. In patients with bronchogenic carcinomas treatment is more complicated and prognosis is often poor. Treatment aims to return plasma osmolality to normal without causing further expansion of the extracellular fluid compartment (this, however, occurs in cases when hyperosmotic solutions are given).

Fluid restriction is the simplest form of treatment, but in the long term the excessive thirst associated with this treatment may be difficult to manage.

If plasma osmolality is low and rapid correction is required, diuretics such as furosemide or ethacrynic acid can be employed. These agents prevent the concentration gradient in the medulla from building up and thus decrease the effectiveness of vasopressin. Because diuresis is accompanied by significant urinary losses of potassium, calcium and magnesium, these electrolytes should be replaced by intravenous infusion.

In an emergency situation with severe hyponatremia, hypertonic saline (3%) or normotonic saline (0.9%) may be administered intravenously. However, this must be done with caution, since fluid overload may precipitate heart failure or circulatory collapse, and overly rapid correction may cause central pontine myelinolysis.

Drugs that reduce the effect of vasopressin on the kidney may be useful, too. Demeclocycline 1-2 g/d orally, causes reversible form of nephrogenic diabetes insipidus, countering the effects of SIADH. However, demeclocycline is nephrotoxic, and renal function must be monitored carefully.

Lithium carbonate has a similar effect, but therapeutic doses are so close to the toxic dose that it is rarely used.

Educational objective: Review the self-limited hyperkalemia in patients with trauma.

Self-limited hypokalemia occurs in 50-60% of trauma patients--perhaps related to enhanced release of epinephrine. The above effect is transient. Other causes of hypokalemia are extrarenal potassium loss and renal potassium loss. Urinary potassium is low (< 20 meq/l) as a result of extrarenal loss (diarrhea, vomiting), and inappropriately high (40 meq/l) with urinary loss (mineralocorticoid excess). Hematoma formation cannot cause hypokalemia. Respiratory alkalosis can cause hypokalemia by intracellular shift but this patient’s ABG is not consistent with respiratory alkalosis.

Educational objective: Review the features of poststreptococcal glomerulonephritis.

This patient presents with acute renal failure due to post streptococcal glomerulonephritis. It commonly appears after pharyngitis or impetigo. It accounts for about 5% of the cases of intrinsic renal failure. In acute poststreptococcal glomerulonephritis there is a fall in glomerular filtration rate. The BUN, Cr ratio will typically exceed 20:1 owing to increased urea reabsorption. Another useful index is FeNa (fractional excretion of sodium). With decreased glomerular filtration ratio (GFR), the kidney will reabsorb salt and water avidly if there is no intrinsic tubular dysfunction. Those patients should have a low FeNa (<1%). Oliguric states are more accurately assessed with FeNa than non-oliguric because the kidneys are not so avid for water and sodium as in non-oliguric states. Also in acute renal failure due to poststreptococcal glomerulonephritis UNa is usually below 20 mmol/l and urinary osmolality is over 500mosm/l.

Educational objective: Review the features of renal atheroembolic disease.

Atheroembolic renal failure can occur spontaneously but is most often associated with recent aortic instrumentation. The emboli are cholesterol-rich and lodge in medium and small renal arteries, leading to an eosinophil-rich inflammatory reaction. The urine analysis in atheroembolic acute renal failure is usually normal but may contain eosinophils and eosinophil casts. The diagnosis can be confirmed by renal biopsy, but this is often unnecessary when other stigmata of atheroembolic disease are present (livedo reticularis, distal peripheral infarcts, eosinophilia).

Educational objective: Review the causes of hyponatremia.

This 74-year-old woman has euvolemic hyponatremia because she has normal vital signs and nothing to suggest extracellular fluid (ECF) depletion or excess. The following conditions can cause hyponatremia with normal ECF volume: the syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, glucocorticoid deficiency, pharmacologic agents, and primary polydipsia. In this patient, the correct answer, diuretic-induced hyponatremia, is suggested by the history of a recent change in her antihypertensive regimen, as well as by the mild hypokalemia. The clinician should recall, however, that plasma aldosterone is increased in many patients with SIADH, accounting for the absence of low serum bicarbonate level and for the frequent presence of hypokalemia even in patients not receiving diuretics. Hydrochlorothiazide is a frequent cause of drug-induced hyponatremia in elderly persons. Brain metastasis with SIADH could cause a similar pattern of laboratory abnormalities, but in this patient there is no history of any other symptoms leading to this diagnosis. Patient does not have symptoms of hyperglycemia or hypothyroidism.

Educational objective: Review therapy of diuretic-induced hyponatremia.

The goals of therapy are threefold:
1- to raise the plasma Na by restricting free water intake and promoting free water loss
2- to replace the Na or K deficit or both, and 3- to correct the underlying disorder. Mildly symptomatic hyponatremia is treated by Na repletion, generally in the form of normal saline, in order to avoid rapid changes in fluid volumes. The plasma Na should be raised by no more than 0.3 mmol/l/hour and should not exceed 8 mmol/l during the first 24 hours. Hypertonic saline is reserved for treatment of acute and severe symptomatic hyponatremia.

Educational objective: Review the features of HIV nephropathy.

HIV infection has been associated with focal segmental glomerulosclerosis, acute diffuse proliferative glomerulonephritis, and mesangioproliferative glomerulonephritis, including IgA nephropathy, MPGN, and membranous glomerulopathy. The classic and most common HIV–associated glomerulopathy is focal and segmental glomerulosclerosis (FSGS), an entity that is termed human immunodeficiency virus associated nephropathy (HIVAN). The latter may be the first manifestation of infection in otherwise asymptomatic patients. HIVAN is more common in blacks than in other ethnic groups and is more frequent in intravenous drug abusers with HIV infection than in homosexuals. The disease has been described in all high-risk groups, however, including infants of HIV positive mothers. The typical clinical correlates of HIVAN are severe nephritic syndrome and rapid progression to end stage renal disease, occurring in weeks to months. There is no proven therapy for HIVAN. Anecdotal reports suggest a benefit of steroids, ACE-inhibitors, and zidovudine in reducing proteinuria, but there are no controlled trials to support their use.

Educational objective: Review renal involvement in patients with subacute bacterial endocarditis.

Immune complex glomerulonephritis is a relatively frequent complication of infective endocarditis. Other mechanisms of renal injury in bacterial endocarditis include embolic renal infarction, septic abscesses, acute tubular necrosis secondary to septicemia and drug therapy, disseminated intravascular coagulation and antibiotic induced interstitial nephritis, and, of course, amyloidosis, as in any chronic infection. Renal biopsy reveals mild focal proliferative glomerulonephritis with mesangial and capillary wall deposition of IgG and C3 by immunoflourescence microscopy and subendothelial, mesangial, and subepithelial electron dense deposits by electron microscopy. Endocarditis- associated glomerulonephritis typically has a good prognosis and resolves with the eradication of the underlying infection.

Educational objective: Recognize features of preexisting renal disease in pregnant female vs. pre-eclampsia.

In this 27-year-old pregnant woman pre-eclampsia is highly unlikely by definition because it is a complication that presents after 20 weeks of gestation. This suggests that the abnormal proteinuria in this patient is associated with another disease. The finding of 3+ proteins on dipstick urinalysis is not specific, but the hematuria and erythrocyte casts suggest underlying glomerulonephritis rather than pre-eclampsia.

The markedly elevated 24-hour urine protein excretion in the nephrotic range in this patient is inconsistent with kidney injury due to malignant hypertension.

Clinical features of interstitial nephritis include fever, arthralgias, rash and peripheral blood eosinophilia. Urine often contains WBC and WBC casts. Also it is associated most frequently with medication use.

Educational objective: Review therapy of hypertension in pregnancy.

Patients with renal problems and hypertension will benefit from aggressive treatment of their high blood pressure. The medication of choice during pregnancy is methyldopa. Therefore, this 27-year-old pregnant woman with severe hypertension should receive treatment of her hypertension.

Diuretic agents may be used with caution in patients with hypertension and preexisting renal disease, especially in the presence of marked peripheral edema, in patients who were effectively treated with such agents before the beginning of pregnancy, or when therapy was started before 20 weeks of gestation with beneficial results. Diuretic agents should be discontinued if pre-eclampsia develops or in the presence of reduced fetal growth. A renal biopsy can be used to confirm or rule out the diagnosis of pre-eclampsia but this is not a consideration in this case. Outcomes in pregnant patients with chronic renal disease but well-preserved renal function (serum creatinine concentration <2.0 mg/dL) are generally good.

Abortion is not indicated for medical reasons in this patient.

Educational objective: Review features of analgesic nephropathy.

This man with chronic low back pain most probably uses analgesic medications on a regular basis. Analgesic nephropathy is a distinct clinicopathologic syndrome that has been described in heavy users of analgesic mixtures containing phenacetin in combination with aspirin, acetaminophen or caffeine. Morphologically analgesic nephropathy is characterized by papillary necrosis and tubulointerstitial inflammation. The intake of 1.0 g phenacetin per day for one to three years or the total ingestion of 2 kg phenacetin in combination with other analgesics appears to represent minimum requirements for the development of analgesic nephropathy. More than half of the patients with analgesic nephropathy have pyuria, which, if persistently associated with sterile urine, provides an important clue to the diagnosis. Proteinuria, if present, is typically mild (less than 1 g/day). Patients with analgesic nephropathy are usually unable to generate maximally concentrated urine, reflecting the underlying medullary and papillary damage. Transitional cell carcinoma may develop in urinary pelvis or ureters as a late complication of analgesic abuse.

Educational objective: Review therapy for renal involvement in patients with SLE.

Patients present with nephritic syndromes. If urinary abnormalities are detected, renal biopsy is often performed.

Five patterns of renal disease are seen on biopsy:

Individuals with type I and II disease require no treatment. Patients with extensive type III lesions and all type IV lesions should receive aggressive immunosuppressive therapy. Corticosteroids are the mainstay of treatment (methylprednisolone 1 gm intravenously daily for three days followed by prednisone 60 mg orally daily for four-six weeks) but are associated with many side effects. Cyclophosphamide can be added for patients with inadequate renal response or aggressive lesions. Cytotoxic agents appear to improve long-term renal survival in those with type IV nephritis.

Educational objective: Review features of medullary sponge disease of the kidney.

This 39-year-old woman presents with the symptoms, signs and radiologic findings of medullary sponge disease (MSK). MSK is a congenital disorder. Most of the cases are sporadic. Males and females are affected equally. The pathologic lesion is cystic dilation of the inner medullary and papillary collecting ducts; with collecting diameters ranging from 1 to 5 mm. Calculi are frequently found in the dilated collecting ducts.

Patients generally present in the third or fourth decade with kidney stones, infection and recurrent hematuria. The disease is most commonly diagnosed by an intravenous pyelogram which shows linear striations radiating into the renal papillae or small cystic collections of contrast in the dilated ducts. Proteinuria is minimal if present at all, and renal function is normally preserved unless there is renal damage from recurrent infection or severe stone disease.

Asymptomatic patients require no specific therapy except maintainance of high fluid intake to reduce the risk of nephrolithiasis. Infections should be treated aggressively, and instrumentation of the urinary tract should be minimized to avoid introducing infection.

The lesion depicted in the picture is most likely a simple renal cyst. (It is round, hypoechogeneic, with no echoes from the lesion and with enhancement of the posterior wall – all three features are ultrasonographic criteria for distinguishing between solid masses and cystic lesions). Simple renal cysts are the most common renal masses (65-70%) and seen most often in patients over the age of 50.

Bilateral cysts are much less common than unilateral and are really rare in subjects under the age of 50. They are typically asymptomatic and discovered incidentally. Most common complications are cyst infection and, rarely, angiotensin-dependent hypertension. Differentiation from polycystic kidney disease and carcinoma is important.

Bilateral cysts in young patients suggest polycystic disease.

The condition demonstrated in this picture is polycystic kidney disease (despite the name, the cysts may be seen in the liver, pancreas and spleen). In overt disease (like this one) diagnosis is easy since enlarged kidneys containing multiple cysts are easily demonstrated by ultrasonography or CT-scanning. Hepatic cysts are seen in about one half of patients (usually females over age 40).

Other extrarenal manifestations of polycystic kidney disease include colonic diverticula, umbilical and inguinal hernia, cardiac valve diseases (25-30% of cases – mitral valve prolapse and aortic regurgitation are most common) and cerebral aneurysms (4-10% of patients - leading to subarachnoidal hemorrhage).

Condition represented in the photograph is polycystic kidney disease. This disease progresses to end stage renal disease in a majority of patients. This occurs most commonly in middle age and later (2% below age of 40, 20-25% by age 50 and 50-75% by the age of 75).

Risk factors for more rapid progression are as follows: younger age at presentation, male gender, genetic abnormality, episode of gross hematuria, hypertension, increased renal size, and Black race. Polycythemia and renal cancer are rare complications. Hepatic carcinoma is not particularly associated with polycystic kidney disease.

Hepatic rupture may be more common in these patients, but there is no data confirming this possibility.

Educational objective: Review of risk factors for nephropathy in diabetic patients.

Educational objective: Understand the mechanism of action for furosemide.

Loop diuretics reduce NaCl reabsorption by inhibiting Na-K-2Cl carrier in the luminal membrane in the thick ascending limb of the loop of Henle. The efficacy is dose-related and depends on delivery of the diuretic to the site of action. Loop diuretics are highly protein bound and are therefore delivered mostly by tubular secretion rather than by glomerular filtration.

In subjects with normal renal function, diuretic effect can be seen with as little as 10 mg of furosemide given orally. Maximal effect is seen with about 40 mg given intravenously. The maximum effective dose, however, is higher in patients with heart failure, advanced cirrhosis, or renal failure. In these conditions, decreased renal perfusion (with decreased drug delivery), diminished tubular secretion (because of retention of the anions in renal failure), and enhanced activity of the rennin-angiotensin-aldosterone system (enhancing sodium retention) combine to diminish the diuretic effect.

Educational objective: Review of causes of acute renal failure during hospitalization.

Causes of acute renal failure in tertiary hospital centers

Acute tubular necrosis (ATN) - 45%
Prerenal - 21%
Acute on chronic RF – mostly due ATN and prerenal - 13%
Urinary tract obstruction - 10%
Glomerulonephritis or vasculitis - 4%
Acute interstitial nephritis - 2%
Atheroemboli - 1%

Educational objective: Differentiation between ATN and prerenal azotemia.

Differentiation between ATN and prerenal acute renal failure can be accomplished usually by complete examination of urine and by serial measurements of the BUN and plasma creatinine levels. The BUN/plasma creatinine ratio is typically in the <20:1 range in ATN but is often over 20:1 in the cases of prerenal failure.

Urinalysis is normal or near normal in prerenal failure, while classic findings in ATN are muddy brown granular and epithelial cell casts and free epithelial cells.

Urine sodium concentration tends to be low in prerenal failure (<20 meq/l) in an appropriate attempt to conserve sodium, and will be high (>20 meq/l) in ATN in part due to the tubular injury. Fractional sodium excretion is consequently low in prerenal cases (<1%) and higher (>1%) in ATN.

Loss of concentrating ability is almost universal in ATN with urine osmolality being below 300-350 mosm/kg in almost all cases and most commonly below 350 kg/kg. Urine osmolality in prerenal azotemia is most commonly >400 mosm/l.

Urine plasma concentration/plasma creatinine concentration ratio is another measure of the water reabsorption (initially glomerular filtrate and plasma have the same concentration of creatinine but later by the water reabsorption of water urine creatinine concentration rises). In the prerenal azotemia most of the filtrated water is reabsorbed resulting in a ratio of above 40, while water reabsorption is less efficient in ATN, resulting in a ratio usually below 20. Rate of the plasma creatinine concentration rise may also be helpful and is generally faster with ATN (> 0.3-0.5 mg/dl/day) than in cases of prerenal renal failure in which case it is slower and fluctuating (due to differences in renal perfusion over time).

Educational objective: Understand hypokalemia of diuretic therapy.

Hypokalemia is a relatively common problem with diuretic therapy. Increased delivery of sodium and water to the aldosterone sensitive potassium secretory site in the collecting tubule is partially responsible for hypokalemia. Another mechanism is increased aldosterone secretion due to hypovolemia induced by diuretics. As with other diuretic-induced fluid and electrolyte complications, potassium loss occurs only during the first two weeks before a new steady state is established.

So, a patient with normal potassium levels at the end of third week is not at risk for late hypokalemia unless diuretic dose or extrarenal potassium loss is increased, or dietary potassium intake is reduced. Hypokalemia can lead to cardiac arrhythmias (especially in patients on digitalis therapy) and is thus especially dangerous in patients with underlying heart disease (also hypertension and hepatic cirrhosis).

Loop diuretics are more potent than thiazide ones in diuretic effects but produce less hypokalemia (exact reason for this is not known).

Educational objective: Review causes of pseudohyperkalemia.

Pseudohyperkalemia refers to elevation of the measured plasma potassium level because of the potassium movement out of cells during or after a blood specimen has been drawn. The most common cause is mechanical trauma to red blood cells during the venipuncture (hemolysis). It can also occur in hereditary spherocytosis and in familial pseudohyperkalemia in which there is increased temperature-dependent leakage of potassium out of red blood cells after the specimen is collected.

Potassium also moves out of white blood cells and platelets after clotting has occurred (0.1-0.5 meq/l in normal subjects). In cases of marked leukocytosis (100,000 per mm3) and thrombocytosis (400,000 mm3) as in the cases of leukemia or myeloproliferative disease, the measured potassium may be up to 9 meq/l. For every 100,000 mm3 increases in platelets, count serum potassium rises for about 0.15 meq/l.

Pseudohyperkalemia should be suspected in all patients in whom there is no apparent reason for potassium level elevation, and in asymptomatic patients.

Educational objective: Review features of renal tubular acidosis.

This patient most likely has renal tubular acidosis type 1 (RTA 1) secondary to Sjögren’s syndrome. RTA 1 is in most instances a secondary disorder and associated with such conditions as Sjögren’s syndrome, lupus, chronic active hepatitis, and hypergammaglobulinemia. A minority is inherited, most commonly as an autosomal dominant trait; but X-linked, autosomal recessive, and sporadic cases have been described.

RTA 1 is a disorder of the distal nephron in which there is either deficiency in hydrogen ion secretion from the blood to the urine, or increased back-diffusion of hydrogen ions back to the blood. This result in decreased daily acid secretion and leads to metabolic acidosis. Acidosis is hyperchloremic metabolic acidosis (normal anion gap), and is associated with hypokalemia. Despite acidosis, urine cannot be maximally acidified and urinary pH is always over 5.5. Because of acidosis, renal tubule calcium reabsorption is diminished, resulting in hypercalciuria and diminished citrate excretion. This leads to development of renal stones and nephrocalcinosis. Rickets may develop in children, and osteomalacia in adults. Fractional excretion of bicarbonate is always below 10% (to compensate for acidosis).

RTA 4 is associated with hypoaldosteronism and is associated with hyperkalemia. In this disorder urinary pH may be lower than 5.5, and there is no association with nephrolithiasis.

Ingestion of acids leads to high anion gap metabolic acidosis; there are no reasons to suspect this form of acidosis in this patient. Chronic obstructive pulmonary disease leads to respiratory acidosis, which is usually well compensated. Acidosis of renal insufficiency is seen in end-stage renal disease.

Educational objective: Review clinical and laboratory features of hyperkalemia.

The patient in this question has end stage renal disease and is on hemodialysis. These patients are prone to hyperkalemia due to their renal insufficiency. He also missed his last dialysis, which makes electrolyte imbalances even more probable. His symptoms of the weakness and numbness are characteristic of hyperkalemia, as are described EKG changes.

Hyponatremia may cause weakness, but it is highly unlikely to present with high peaked T-waves and prolongation of QRS in the EKG.

Diabetic polyneuropathy is most commonly characterized by the lancinating pains that first occur in the areas of the body innervated by the longest nerves (lower legs), and is unlikely to present with a relatively sudden onset of muscle weakness and numbness.

Hyperacute myocardial infarction is a possibility in this kind of presentation but is much less likely, especially considering duration of symptoms.

Hypokalemia is characterized by flattening of the T-waves in EKG and also muscle weakness and cardiac arrhythmias.

Educational objective: Recognize the most common presentation and form of IgA nephropathy.

This patient most likely suffers from IgA nephropathy – Berger’s disease (most common glomerulopathy worldwide – 10-40%). There is no proven therapy for IgA nephropathy, although there is suggestion that fish oil may be beneficial. Berger’s disease usually smolders for decades with episodes of exacerbations of hematuria and renal impairment during intercurrent infections. Long-term prognosis is generally good with 20-50% of patients developing end stage renal disease over a 20-year period. Clinical predictors of a more aggressive course of disease include male sex, advanced age, renal insufficiency, nephrotic range proteinuria and hypertension at presentation.

Educational objective: Recognize features of renal tubular acidosis type 1.

This patient suffers from renal tubular acidosis that is caused by intravenous administration of amphotericin B, which causes renal insufficiency with disproportional metabolic acidosis. Amphotericin induced renal tubular acidosis is of type 1. This type is due to a defect in distal tubular acidification of urine, and its hallmark features include the following: hyperchloremia, normal anion gap, and inability to maximally acidify urine (to pH-5.0) despite degree of metabolic acidosis

Educational objective: Review risk factor for calcium renal stones.

Renal stone formation occurs when normally soluble material (e.g. calcium) supersaturates in the solution (urine). Microcrystals form and attach to the urinary mucosa (most commonly to the end of the collecting duct). There stones gradually increase in size over time.

There are several risk factors for development of renal stones and they include hypercalciuria, hyperuricosuria, hypocitraturia (rather than hypercitraturia), high dietary protein intake and low intake of fluids (water). Urinary citrate helps to keep calcium in the solution and diminishes the likelihood for stone development.

Other risk factors are prior history of calcium nephrolithiasis, family history, increased enteric oxalate absorption (short bowel syndrome), urinary tract infection, hypertension, vasectomy and therapy with sulfadiazine and triamterene.

Educational objective: Review features of renal failure associated with multiple myeloma.

Renal failure is not rare in patients with multiple myeloma. This is especially true for those patients having hypercalcemia or those forming excess light chains and therefore developing myeloma kidney, primary amyloidosis, or light chain deposition disease. Renal failure is typically associated with low anion gap (as in the option D of our question). This phenomenon is caused by a large amount of positively charged proteins in the patient’s blood that are not measured.

Patients with bacterial endocarditis may develop the following forms of renal disease: renal embolic disease, post-infectious immune complex-mediated glomerulonephritis, and drug-induced acute interstitial nephritis.

Renal embolism is suggested if there is acute, most commonly unilateral flank pain even several months after bacteriologic cure of the endocarditis. This condition may be demonstrated by perfusion defect on renal radionuclide scan, and may be associated with other embolic phenomena.

Immune complex-mediated glomerulonephritis has clinical manifestations similar to other forms of acute glomerulonephritis, hematuria, red cell and other cellular casts in association with varying degrees of hypertension and renal insufficiency. Nephrotic syndrome is unusual.

The interstitial nephritis shares many of the clinical findings of the glomerulonephritis, hematuria, mild proteinuria and renal insufficiency, but no red blood cell casts. The distinction also may be made based on the timing of the renal insufficiency development. Glomerular disease usually peaks just before the institution of appropriate antibiotic therapy, while acute interstitial nephritis occurs after institution of antibiotic therapy, requiring ten or more days of treatment. It is also associated with fever, eosinophilia and eosinophiluria

Patients with bacterial endocarditis may develop the following forms of renal disease: renal embolic disease, post-infectious immune complex-mediated glomerulonephritis, and drug-induced acute interstitial nephritis.

Renal embolism is suggested if there is acute, most commonly unilateral flank pain even several months after bacteriologic cure of the endocarditis. This condition may be demonstrated by perfusion defect on renal radionuclide scan, and may be associated with other embolic phenomena.

Immune complex-mediated glomerulonephritis has clinical manifestations similar to other forms of acute glomerulonephritis, hematuria, red cell and other cellular casts in association with varying degrees of hypertension and renal insufficiency. Nephrotic syndrome is unusual.

The interstitial nephritis shares many of the clinical findings of the glomerulonephritis, hematuria, mild proteinuria and renal insufficiency, but no red blood cell casts. The distinction also may be made based on the timing of the renal insufficiency development. Glomerular disease usually peaks just before the institution of appropriate antibiotic therapy, while acute interstitial nephritis occurs after institution of antibiotic therapy, requiring ten or more days of treatment. It is also associated with fever, eosinophilia and eosinophiluria.

Educational objective: Review laboratory features of acute poststreptococcal glomerulonephritis.

Poststreptococcal glomerulonephritis is caused by specific nephritogenic strains of group A, â-hemolytic streptococci. Children below 7 years of age are at highest risk, and incidence is higher after skin infections (25%) than after pharyngitis (5-10%). It occurs typically about 10 days after pharyngitis and 21 days after impetigo.

Renal failure is usually moderate, transient, and associated with only mild (if any) metabolic acidosis; the anion gap is only slightly, if at all, elevated.

Of the offered options in the questions only option E fulfills these criteria.

Educational objective: Review of diagnosis for significant microalbuminuria in diabetic patients.

A 24-hour urine collection is the best method for detection of microalbuminuria (gold standard). However, collection is cumbersome and often not complete. Because of this, screening for microalbuminuria is usually performed using either timed urine collection or an early morning specimen to minimize changes in the urine volume production that are common during the day. Random urine specimen is still used despite all the drawbacks. Microalbuminuria is unlikely if albumin excretion is below 20 ìg/min in a timed urine sample or if concentration is less than 20-30 mg/l in a random specimen. Higher values (especially just a little above these values) may represent false positive findings and should be confirmed by a 24-hour urine collection.

Microalbuminuria is not an indication of either renal biopsy or renal ultrasound.

Educational objective: Emphasize importance of the patient’s autonomy.

The patient in question is clearly not incompetent to make decisions on his own behalf, and his wishes should be respected. Health care providers have responsibility to their patients, and it is unethical to comply with wishes of the family against patient’s own wishes. Determination of whether or not the patient is competent for making decisions can only be made by legal authority (court), but in this case there is no grounds to ask for such a decision because the psychiatrist (who has a purely advisory role) has assessed the patient to be fully competent.

Educational objective: Illustrate relation of microalbuminuria to renal histology.

Renal biopsy in diabetic patients with microalbuminuria may vary from relatively normal histologic findings to the clear evidence of diabetic nephropathy. Classical description of focal segmental glomerulosclerosis is not, however, seen in the majority of the patients with overt diabetic nephropathy (this form of the histologic changes is pathognomonic, however).

Normal renal histology is the most common finding in renal biopsy of the patients with microalbuminuria below 45 mg/day.

All of the above can result in Rhabdomyolysis.

Granular casts are from protein deposits and degenerating cellular elements.

Triple phosphate crystals are shown, the urine must be alkalinefor crystal formation.

Classic Trichomonas in urine. The infection is frequently asymptomatic in men and women.

These structures, dysmorphic erythrocytes in urine, are more closely associated with glomerular disease.

Muddy brown casts are associated with ATN. Please remember this!!

The leukocyte cast is an indication of infection in the renal parenchyma.

Ironically enough, proteinuria is an independent predictor of all of them, and should prompt a work up including screening the heart and vascular system.

Diabetes: 45% Hyperension: 26% Glomerulonephritis:9% Misc:15% Unknown: 5%

>3 grams/24hrs associated with hypoalbuminemia and edema.

The absence of sinus disease rules out Wegener's Granulomatosis.