The correct answer is 4. What is not very clear to me is "routine urinalysis" because it is not usually done in an asymptomatic healthy child. Microhematuria without associated symptoms may be a finding without pathologic significance and must be confirmed in a subsequent new sediment (although I do not know if at 15 days or later).

[HIDDEN] What is not very clear to me is "routine urinalysis" because it is not usually done in an asymptomatic healthy child. Microhematuria without associated symptoms may be a finding without pathologic significance and must be confirmed in a subsequent new sediment (although I do not know if at 15 days or later).

A 10-year-old girl comes for a health check-up. Physical examination is normal with weight and height in the 50th percentile and BP 109/65. A routine urinalysis shows a specific gravity of 1035 pH6 blood 2+ with no protein. Urine sediment shows 5-10 red blood cells per field. What would be the most appropriate course of action?

Determination of creatinine and nitrogen in blood.

Determine antinuclear antibodies and complement.

[Acute tubulointerstitial nephritis in children].

Acute tubulointerstitial nephritis (ATIN) is a rare renal disorder in children. Patients usually present non-specific symptoms and signs so that the diagnosis of ATIN is often delayed. The disease may be infection- or drug-induced or it may occur without a known cause. Early recognition and appropriated therapy usually lead to an excellent prognosis. The aim of the study was to describe clinical and laboratory findings and the course of ATIN in 21 patients, that are typical enough to enable early recognition of the disease as it is potentially reversible. Between 1986 and 1997 we observed 21 patients, aged 7-16 years (mean, 12.8), with acute tubulointerstitial nephritis, including eight with tubulointerstitial nephritis and uveitis (TINU syndrome). Laboratory studies included urinalysis, complete blood count, erytrocyte sedimentation rate (ESR), plasma creatinine, glomerular filtration rate (GFR), electrolytes, proteins, IgG, C3, C4 antinuclear-antibodies (ANA), antistreptolysin-O and antibodies to hantaviruses. Renal ultrasound was done in all patients. Renal biopsy was performed in 5 children. All children had previously been healthy. The symptoms of ATIN developed within a few days (Table 1). The most common initial symptoms were fatigue, fever, gastrointestinal disturbances, anorexia and weight loss. Less common complaints included headache, arthralgias and maculopapular rash. On addmition no patient had hypertension, oedema or evidence of acute infection. ESR, plasma urea and creatinine concentrations were increased in all, plasma proteins and IgG levels in the majority of patients. ANA were negative in 15 pts in whom this analysis was performed; C3 and C4 levels were normal. In two children recent strepococcal and in the other 6 hantavirus infection was serologicaly proved. All patients had non-oliguric acute renal failure (ARF): GFR was 21.7 +/- 8 9 in 14 pts and 67 +/- 9.7 in 7 pts. Low urine specific gravity (1003-1014), mild proteinuria (0.3-0.4 g/24 h), leukocyturia and/or haematuria were found in all patients; glycosuria, aminoaciduria and decreased tubular reaposrption of phosphate (TRP) were found in 12/21, 9/21 and 9/14 patients, respectively. Urine cultures were negative in all children. Renal US demonstrated enlarged hyperechoic kidneys in 11 pts, in remaining 10 pts no abnormalities were found. Renal biopsy, performed in 5 children, confirmed the diagnosis of ATIN. Eight patients subsequently developed anterior uveitis as part of TINU syndrome. Treatment included supportive therapy in all and six patients received prednisolone for 4-8 weeks (40-60 mg/m2/24 h for 10-14 days with subsequent reduction of dose over several weeks). Anterior uveitis was successfully treated with topical steroids. Renal function completely recovered in all patients: GFR (109 +/- 22.6 ml/min) within a mean interval of 47 +/- 33 days, concentration ability within 2-12 (mean 4.5) months. Common clinical features of ATIN are non-oliguric acute renal failure of various degrees, signs of tubular dysfunction, proteinuria, haematuria, leukocyturia and absence of hypertension. All our patients had normal blood pressure, non-oliguric renal failure, proteinuria, hypostenuria and abnormal urinary sediment; about half of them had glycosuria and/or other signs of proximal tubular dysfunction. The most important causes of ATIN in children reported in literature are systemic infections and drugs. However, the cause of ATIN in our patients was assessed as being related to infection only in 8 patients and to diclofenac in one. No infection, drug, toxin or other cause could be identified in 4, as well as in 8 pts with TINU syndrome. The prognosis of ATIN in children is considered to be favourable, but some patients may develop chronic renal failure. Renal function completely recovered in all our patients; that is consistent with outcome data from the most reports. Acute tubulointerstitial nephritis is an important cause of ARF in children, its aetiology may be different and it carries an excellent prognosis. ATIN should be suspected in a child who presents typical, although non-specific symptoms and signs, associated with lukocyturia and/or microhaematuria, signs of tubular dysfunction and unexplained renal failure. The diagnosis can be verified at renal biopsy. Early recognition of the disease is important to remove possible aetiologic agents and to treat them before chronic lesions are present to avoid long-term renal damage.

Cases from the Osler Medical Service at Johns Hopkins University. Antiglomerular basement membrane disease.

A 47-year-old Taiwanese man with no notable medical history was admitted with low-grade fevers and night sweats that had persisted for 5 to 6 weeks. An extensive investigation at another hospital could not determine the cause of the fevers, but documented acute renal failure with a blood urea nitrogen level of 60 mg/dL and a serum creatinine level of 5.6 mg/dL. He was admitted to the Johns Hopkins Hospital for further evaluation.The patient, who had been living in the United States for the past 20 years, reported no recent travel and no behaviors that are associated with transmission of human immunodeficiency virus. He was not taking any medications, and he denied using herbal or nutritional supplements. He had no recent weight loss. There were no specific complaints on review of systems. On physical examination, he was a thin, middle-aged man in no distress. Vital signs included a temperature of 37.5 degrees C, a blood pressure of 166/86 mm Hg, a pulse of 70 beats per minute, a respiratory rate of 16 breaths per minute, and 99% oxygen saturation on room air. Sclera were anicteric, and he had no palpable adenopathy. His lungs were clear, and his heart rate was regular without extra sounds. His abdomen was thin, nontender, and without masses or organomegaly. There was no edema or signs of embolism in the extremities. Laboratory studies revealed a white blood cell count of 14,200/mL(3), a hematocrit of 23.1%, and a platelet count of 456,000/mL(3). Blood chemistries were notable for a blood urea nitrogen level of 61 mg/dL and a serum creatinine level of 7.6 mg/dL. Levels of aminotransferases, total bilirubin, and alkaline phosphatase were within normal limits. Urinalysis revealed large hemoglobin, 1+ protein, numerous red blood cells, and 3 to 5 white blood cells. Numerous red blood cell casts were seen on microscopic examination of the urine sediment. The patient's erythrocyte sedimentation rate was >130 mm/h, and his C-reactive protein level was elevated at 12.6 mg/dL. Serologies were negative for antinuclear antibodies and antineutrophil cytoplasmic antibodies; serum complement levels were normal. What is the diagnosis?

Microscopic hematuria is associated with low bone mineral density in aged women and men.

Little is known concerning renal or urological risk factors for osteoporosis. The aim of this study was to explore an association between urinalysis and bone mineral density (BMD) in 4,835 Japanese adults. Participants were 4,835 individuals (female 3,683; male 1,152) aged 50 years and over who received a health check-up between January 1995 and March 2006 in Japan. BMD of the distal radius and ulna of the non-dominant forearm was measured by the dual-energy X-ray absorptiometry (DXA) method using a DTX-200 Dexacare osteometer (Osteometer MediTech A/S, Rødovre, Denmark). Urine variables were protein, and red blood cells (RBCs) and white blood cells (WBCs) in urine sediment (categorized as <1, 1-4, 5-9, or >or=10 cells per high-power microscopic field). Average age was 58.9 years (SD 5.6) in women, and 60.5 years (SD 6.2) in men. Simple linear regression analysis showed that urinary RBCs were associated with BMD in women (beta = or-5.88 x 10(-3), R (2) = 0.004, p < 0.0001) and men (beta = or-1.34 x 10(-2), R (2) = 0.013, p = 0.0001). These associations held when possible confounders were adjusted (beta = or-2.05 x 10(-3), R (2) = 0.001, p = 0.0338 for women and beta =or -5.67 x 10(-3), R (2) = 0.006, p = 0.0163 for men). Microscopic hematuria is associated with forearm BMD in women and men aged 50 years and over. Further studies should be conducted to determine the mechanisms underlying this association.

Limited evaluation of microscopic hematuria in pediatrics.

The purpose was to determine the value of the standard laboratory and radiologic evaluation of microscopic hematuria in children, and to determine the prevalence of idiopathic hypercalciuria in those children referred for evaluation of unexplained microscopic hematuria. This was a retrospective study of 325 children referred from 1985 to 1994 for the evaluation of asymptomatic microscopic hematuria. The diagnostic studies reviewed included serum creatinine, blood urea nitrogen, serum electrolyte studies, serum complement concentration, antinuclear antibody, urinalysis, urine calcium to creatinine ratios, urinary protein to creatinine ratio and/or 24-hour urinary protein excretion, renal ultrasounds, intravenous pyelograms, voiding cystourethrograms, and historical information. All creatinine and electrolyte values were normal for age, and none of the biochemical tests obtained in the children with hypercalciuria was abnormal. Of the 325 patients with idiopathic microscopic hematuria, only 18 had abnormal renal ultrasound examinations and 9 voiding cystourethrograms showed low-grade reflux. Hypercalciuria was found in 29 patients. The family history was positive for urolithiasis in 16% of patients without hypercalciuria compared with 14% of patients with hypercalciuria. A positive family history of hematuria was reported in 25% of patients; 62 patients did not have hypercalciuria and 4 of the patients had hypercalciuria. Microscopic hematuria in children is a benign finding in the vast majority of children. Our data demonstrate that a renal ultrasound, voiding cystourethrogram, cystoscopy, and renal biopsy are not indicated in the work-up of microscopic hematuria, and microhematuria in the otherwise healthy child is a minimal health threat, rarely indicative of serious illness.

[Adrenal hemorrhage in a patient with systemic lupus erythematosus].

A 58-year-old female was referred to our department with intermittent suffocation for 1.5 years, aggravated for a month. 1.5 years before she developed oral ulcer, raynaud phenomenon, proteinuria, bilateral pleural effusion, ANA and anti-dsDNA positive. This patient was diagnosed with systemic lupus erythematosus (SLE). After given hormones, hydroxychloroquine sulfate (HCQ), her symptom relieved soon. The patient stopped her pills 1 year ago. One month ago, she had chest tightness, increased urine foam, and suffered from oliguria. Her admission medical examination: blood pressure (BP) 130/80 mmHg, conjunctiva pale, and lower lung breath sounds reduced. There was no tenderness, rebound pain and abdominal muscle tension in the abdomen. Liver and spleen rib inferior, mobile dullness negative, and lower extremity edema. Blood routine tests were performed with hemoglobin (HGB) 57 g/L. Urine routine: BLD (3+). 24-hour urinary protein 3.2 g. serum albumin 20.5 g/L, C-reactive protein (CRP) 12.85 mg/L, erythrocyte sedimentation rate (ESR) 140 mm/h. Antinuclear antibody (ANA) (H)1:10 000, anti-dsDNA antibody 1:3 200; anti-Smith antibody, anti-U1-snRNP/Sm antibody were positive, blood complement 3(C3) 0.43 g/L, complement 4(C4) 0.07 g /L. Anticardiolipin antibody (ACL), anti-β2-GP1, lupus anticoagulant (LA) were negative; HRCT suggested bilateral medial pleural cavity product liquid. Admission diagnosis: SLE lupus nephritis, anemia, pleural effusion, and hypoproteinemia. We treated her with methylprednisolone 1 000 mg×3 d, late to 48 mg/d and cyclophosphamide 1.0 g, HCQ 0.2 g bid, gamma globulin 10 g×5 d. Day 2 of treatment, this patient developed acute right upper quadrant pain, not accompanied by nausea, vomiting, blood stool and diarrhea. Antipyretic antispasmodic treatment was invalid, after the morning to ease their own abdominal pain. Day 4 of treatment, daytime blood HGB 77 g/L. Bilateral renal vascular ultrasound: bilateral renal artery blood flow velocity was reduced. The abdominal pain of the above symptoms recurred at night, BP was 120/80 mmHg, and no positive signs were found on abdominal examination. No abnormality was found in the vertical abdominal plain film. Blood routine examination: HGB 53 g/L, Plasma D dimer 2 515 μg/L, amylase in hematuria was normal, the stool occult blood was negative. Abdominal computed tomography (CT): normal structure of right adrenal gland disappeared, irregular mass shadow could be seen in adrenal region, CT value was about 50 HU. Morphological density of left adrenal gland was not abnormal. The retroperitoneum descended along the inferior vena cava to the right iliac blood vessel and showed a bolus shadow. The density of some segments increased. The lesion involved the right renal periphery and reached the left side of abdominal aorta. Most lesions surrounded the inferior vena cava, the right renal vein and part of the small intestine. The boundary between the upper lesion and the vena cava was unclear. Iodinecontaining contrast agent was taken orally. No sign of contrast agent overflowing was found in the abdominal cavity. Hematoma and exudative changes were considered in retroperitoneum. CONCLUSION of contrast-enhanced ultrasound of blood vessels: The retroperitoneal inferior vena cava (volume 3.5 cm×3.5 cm×1.5 cm) was hypoechoic and had no blood flow lesion. The adrenal gland had a high possibility of origin. Left renal vein thrombosis extended to inferior vena cava. According to the above data, it was analyzed that the cause of retroperitoneal hematoma of the patient was left adrenal vein thrombosis caused by hypercoagulable state, which led to vascular rupture and hemorrhage caused by increased vascular pressure in adrenal gland. Therefore, on the basis of continuing to actively treat the primary disease, and on the basis of dynamic observation of no active hemorrhage for 3 days, the anticoagulant therapy was continued with 10 mg/d of apixaban. Clinical symptoms were gradually eased, HGB did not decrease. Two weeks later, the ultrasonic examination showed that the irregular cluster hypoechoic range behind the inferior vena cava was significantly smaller than that before (1.8 cm×1.2 cm×0.7 cm). Abdominal CT examination after 1 month showed that there was no abnormal morphological density of bilateral adrenal glands and basic absorption of retroperitoneal exudation. Adrenal hemorrhage is uncommon. SLE with adrenal hemorrhage is rarer. In SLE patients, especially those complicated with APS, if abdominal pain accompanied by HGB decrease occurs, except after gastrointestinal hemorrhage, the possibility of adrenal hemorrhage should be warned.

Atherosclerotic Renovascular Disease.

The patient, a 78-year-old Asian male, was brought to the hospital because of acute shortness of breath that had progressively worsened over the course of the day. He complained of a nonproductive cough and claudication after walking 1 block. His past medical history was significant for mild renal insufficiency (serum creatinine 1.5--2.0 mg/dl), the etiology of which was never explored. Although there was a recent history of mild to moderate hypertension, at presentation his blood pressure was noted to be 240/118 mm Hg in both arms. His physical exam at the time of admission was remarkable for grade II hypertensive retinopathy, an S4 gallop, periumbilical systolic bruits, audible femoral arterial bruits and absent distal lower extremity pulses. Initial complete blood count, serum electrolytes and cardiac enzymes (including lactate dehydrogenase) were normal. His blood urea nitrogen and serum creatinine concentrations were 51 and 3.6 mg/dl, respectively, and his urinalysis showed 1+ protein (both by dipstick and sulfasalicylic acid) with a "benign" sediment (0--1 WBC/HPE, 1--2 RBCs/HPF) with occasional granular casts. His electrocardiogram, apart from demonstrating left ventricular hypertrophy with secondary ST-T wave abnormalities, showed no acute changes; his chest X-ray demonstrated cardiomegaly and pulmonary vascular congestion. He was intubated and subsequently treated with increasing parenteral doses of furosemide (40--240 mg) and a nitroglycerine drip (up to 15 mcg/min). Over the course of the first 48 h, his blood pressure was gradually lowered to 170/100 mm Hg. His urine output increased from 20 ml/h to 125/ml/h, and his respiratory status improved, allowing him to be extubated. In spite of adequate control of his blood pressure in the ensuing days (150--170/80--90 mm Hg), his renal function continued to deteriorate. Renal sonography (without Doppler) demonstrated a right kidney of 9.6 cm and a left kidney of 9.3 cm in length without evidence of hydronephrosis. Both kidneys were noted to be echogenic. Assays for antinuclear antibodies and antineutrophilic cytoplasmic antibodies were negative, and the patient's serum complement levels were normal. For several days after his admission, his serum creatinine gradually rose to 10.7 mg/dl, and hemodialysis was initiated for uremic encephalopathy. Because of the high index of suspicion for renal artery stenosis as the case of both his hypertension and renal failure, a renal angiogram was performed. It revealed a 90% occlusion of the right renal artery with ostial involvement and a 70% occlusion of the left renal artery; both kidneys had poor distal renal vasculature and there was marked atherosclerotic disease of the aorta. After being hemodialyzed for 3 treatments, his renal function began to improve spontaneously. His serum creatinine returned to 3.4 mg/dl, and a subsequent 24-hour urine demonstrated a creatinine clearance of 20 ml/min and an excretion of 1.2 g of protein. Following his discharge from the hospital, his renal function remained unchanged for 3 years, and his blood pressure was easily controlled on monotherapy with a long-acting calcium channel blocker. He recently died from pneumonia.

Diffuse Proliferative Glomerulonephritis -- Evaluation

A complete blood count showing possible anemia and low platelet count followed by renal function tests with elevated serum creatinine (0.4 mg/dl above the upper limit), blood urea nitrogen levels, and urine analysis positive for urine sediments: red blood cells and casts, white blood cells, granular casts are indicative of a glomerular pathology. For further confirmation, a 24 hours urine protein to creatinine ratio and 24 hours urine sample for protein levels can be done. A protein count of greater than 3.5 g/day is suggestive of nephrotic range proteinuria, which is associated with a worse prognosis. A 24-hour urine sample can be used to calculate creatinine clearance to estimate the eGFR. Renal ultrasound can be done to see the size and confirm the presence of two kidneys and the absence of any obstructive pathology resulting in hydronephrosis. Serum complement (C3 and C4) levels help determine the etiology; low levels are associated with the presence of SLE, cryoglobulinemia, and infectious etiology. [12]

Usefulness of scanning procedures for diagnosis of fever of unknown origin in children.

During a 5-year study period, 109 patients were referred to a large children's hospital for evaluation of prolonged fever of unknown origin, defined as temperature greater than or equal to 38 degrees C (100.4 degrees F) for 3 weeks or longer and negative findings on initial examination. A two-phase protocol of outpatient followed by inpatient diagnostic studies was instituted for most patients. Confirmed diagnoses were achieved in just 36 of these children (33%) in the following disease categories: infectious, 24 (22%); autoimmune, 7 (6%); and neoplastic, 2 (2%). Scanning or special procedures and the number with positive results (in parentheses) were as follows: abdominal ultrasonography, 43 (8); abdominal computed tomography, 14 (3); indium scan 11 (5); gallium scanning, 4 (1), upper gastrointestinal tract series, 13 (2); technetium bone scanning 15 (2); bone marrow examination, 16 (1); and cranial computed tomography, 7 (0). These studies rarely led to an unsuspected diagnosis. It appears most appropriate in evaluating fever of unknown origin in children to obtain only basic laboratory studies such as a complete blood cell count, urinalysis and culture, chest radiograph, tuberculin skin test, and, in the older child, an antinuclear antibody titer. When these test results are negative, almost all children can be observed clinically for progression of illness or a focus that might then direct specific diagnostic procedures.

[Laboratory tests in primary care medicine: "essential laboratory tests" (1). Urinalysis].

Japan Society of Clinical Pathology has formed a committee dealing with "lab. tests in primary care medicine". As the first step, they made "Essential Lab. Tests" which were composed of simple qualitative bed-side tests such as urinalysis, Complete blood count (CBC: Hb, Ht, WBC, RBC), CRP, or ESR (Erythrocyte sedimental rate), A/G ratio and biochemical tests if necessary (Table 1). We have performed "Essential Lab. Tests" on 1,026 outpatients who visited General Medicine Clinic for the first time. They consisted of 456 male (age 13-81), and 526 female (age 10-85). This report is the result of urinalysis from "Essential Lab. Tests" of 1,026 patients. 1) The result showed that overall positivity of the urinalysis was 21.3% (when more than one item of the qualitative tests was positive). 2) There was distinctive difference in the positivity of the urinalysis between the sex; i.e. protein and glucose were about twice frequently positive in male, where as occult blood and WBC (Esterase reaction) were 2-3 times more positive in female. 3) Urine protein shows positive in the individual 10-20 yrs old and more than 50 yrs old in both sexes. 4) Glucose was positive in over 40 yrs in male, and occult blood, 40-50 yrs or older in male. 5) WBC shows positive in all age groups in female and 50 yrs or older in male. 6) Positive WBC patients did not necessarily reflect urinary infection in female but nitrites roughly corresponded with urinary WBC in male of 50 yrs or older, meaning probable urinary infection associated with prostatic hypertrophy. 7) Abnormality of urinary sediment corresponded to the positive occult blood and WBC Erastase. 8) Urinalysis is an useful method of screening in primary care medicine.

Appendicitis

Blood and urine test While there is no laboratory test specific for appendicitis, a complete blood count (CBC) is done to check for signs of infection. Although 70–90 percent of people with appendicitis may have an elevated white blood cell (WBC) count, there are many other abdominal and pelvic conditions that can cause the WBC count to be elevated. Due to its low sensitivity and specificity, on its own, WBC is not seen as a good indicator of appendicitis. A urinalysis generally does not show infection, but it is important for determining pregnancy status, especially the possibility of an ectopic pregnancy in women of childbearing age. The urinalysis is also important for ruling out a urinary tract infection as the cause of abdominal pain. The presence of more than 20 WBC per high-power field in the urine is more suggestive of a urinary tract disorder.

Hematuria

The first step in evaluation of red or brown colored urine is to confirm true hematuria with urinalysis and urine microscopy, where hematuria is defined by three of more red blood cells per high power field. Although a urine dipstick test may be used, it can give false positive or false negative results. In gathering information, it is important to inquire about recent trauma, urologic procedures, menses, and culture-documented urinary tract infection. If any of these are present, it is appropriate to repeat a urinalysis with urine microscopy in 1 to 2 weeks or after treatment of the infection. If the results of the urinalysis and urine microscopy reveal a glomerular origin of hematuria (indicated by proteinuria or red blood cell casts), consultation of a nephrologist should be made. If the results of the urinalysis indicate a non-glomerular origin, a microbiological culture of the urine should be performed, if it has not been done already. If the culture is positive, treatment of the

Hematuria

a female less than 50 years old or a male less than 40 years old; has 3-10 red blood cells per high power field; has not had microscopic hematuria before; and has no other risk factors for urothelial cancer. To be in the intermediate risk category, one must satisfy any of the following criteria: Has smoked 10-30 pack-years; is a female 50-59 years old or a male aged 40-59 years old; has 11-25 red blood cells per high power field; or was previously a low-risk patient with persistent microscopic hematuria and has 3-25 red blood cells per high power field. To be in the high risk category, one must satisfy any of the following criteria: Has smoked more than 30 pack-years; is older than 60 years of age; or has above 25 red blood cells per high power field on any urinalysis. For the low risk category, the next step is to either repeat a urinalysis with urine microscopy in 6 months or perform a cystoscopy and renal ultrasound. For the intermediate risk category, the next step is to perform a

Nephritic syndrome

Blood urea nitrogen (BUN) - Also measured using a BMP or CMP, blood urea nitrogen is an indicator of how much nitrogen is in the blood at the time of the phlebotomy. The kidney is responsible for excreting nitrogenous substances in the urine, so an elevated BUN usually indicates that the kidney is not functioning appropriately. Urine Analysis (Urinalysis) - After the patient provides a urine specimen, it is sent to the lab for analysis using a variety of methods including urine dipstick testing and microscopic examination. Because the kidney is responsible for making urine, analyzing the urine directly can provide crucial data that can help the physician diagnose nephritic syndrome. Some findings on urinalysis that are consistent with nephritic syndrome include red blood cells (hematuria), red blood cell casts, proteinuria, and possibly white blood cells (pyuria).

Clinical utility of a rapid test for uristatin.

Uristatin is a trypsin inhibitor present in urine that is increased in most patients with bacterial or viral infections and in many with inflammatory disorders. We included the assay of uristatin as part of a screening program carried out by pediatricians on 4207 Japanese schoolchildren to judge the ability of uristatin to identify those with an infection and (or) inflammation of any cause. We used urine dipsticks for the assay of uristatin, creatinine, albumin, blood, leukocyte esterase, and protein. We also performed quantitative assays for uristatin and creatinine. Another aim was to estimate the reference range for uristatin in schoolchildren, ages 5 to 14 yr. We prepared dipstick pads that were impregnated with a chromogenic substrate for trypsin and measured the uristatin-caused inhibition of trypsin in urine. We measured creatinine so that the ratio of uristatin to creatinine could be calculated to correct for urine concentration. We obtained quantitative uristatin and creatinine results for 4207 children. Of these, 177 had an abnormal urine dipstick for albumin or blood or protein or leukocyte esterase or a combination of these. We used data from 3622 children to establish the reference range for the uristatin dipsticks. The 3622 were diagnosed by their pediatricians as free from an infection or inflammation of any cause and with normal urine dipstick tests. We recommend an upper reference limit for uristatin by dipstick of < or = 7.5 mg uristatin/g creatinine. The leftover 408 children ( [4207-3622-177] = 408) fell into two groups: 205 with diagnoses of no infection, possible infection, or possible inflammatory disorders. The remaining 203 children were renal disease follow-up cases. The diagnoses were based on a physical examination, microscopic urinalysis plus urine dipstick tests for albumin, blood, creatinine, protein, leukocyte esterase and a complete blood count. In the 205 children, 46 had an abnormal uristatin dipstick test, 39 had an abnormal uristatin by immunoassay, 41 had an abnormal erythrocyte sedimentation rate (ESR), 27 had an abnormal serum C-reactive protein (CRP), and one had an abnormal urine microscopic exam. For the first 938 children in the study, the agreement was 93% of negative dipstick uristatin results and immunoassays. The agreement of positive uristatin dipsticks with immunoassays was 85%. We assumed that the immunoassay results were correct. In the evaluation of 189 children with fever, 62 also had an abnormal uristatin by dipstick. A rapid dipstick test for uristatin read on a reflectance photometer gave values that compared well with a quantitative immunoassay method. The uristatin test is sensitive but not specific for any cause of infection or inflammation. Uristatin is easy to determine and appears to be a better indicator than fever, ESR, or CRP for the diagnosis of an infection or inflammation.

Nephrology

Diagnosis History and physical examination are central to the diagnostic workup in nephrology. The history typically includes the present illness, family history, general medical history, diet, medication use, drug use and occupation. The physical examination typically includes an assessment of volume state, blood pressure, heart, lungs, peripheral arteries, joints, abdomen and flank. A rash may be relevant too, especially as an indicator of autoimmune disease. Examination of the urine (urinalysis) allows a direct assessment for possible kidney problems, which may be suggested by appearance of blood in the urine (hematuria), protein in the urine (proteinuria), pus cells in the urine (pyuria) or cancer cells in the urine. A 24-hour urine collection used to be used to quantify daily protein loss (see proteinuria), urine output, creatinine clearance or electrolyte handling by the renal tubules. It is now more common to measure protein loss from a small random sample of urine.

InternalMed_Harrison

Fever >38.3°C (101°F) on at least two occasions 2. Illness duration of ≥3 weeks 3. 4. Diagnosis that remains uncertain after a thorough history-taking, physical examination, and the following obligatory investigations: determination of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level; platelet count; leukocyte count and differential; measurement of levels of hemoglobin, electrolytes, creatinine, total protein, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, ferritin, antinuclear antibodies, and rheumatoid factor; protein electrophoresis; urinalysis; blood cultures (n = 3); urine culture; chest x-ray; abdominal ultrasonography; and tuberculin skin test (TST). The range of FUO etiologies has evolved over time as a result of changes in the spectrum of diseases causing FUO, the widespread Percentage of Cases Due to Indicated Cause

Nephritic syndrome

Signs and symptoms that are consistent with nephritic syndrome include: Hematuria (red blood cells in the urine) Proteinuria (protein in the urine) ranging from sub-nephrotic (<3.5 g/day) to >10 g/day, although it is rarely above nephrotic range proteinuria levels. Hypertension resting blood pressure is persistently at or above 130/80 or 140/90 mmHg. Blurred vision Azotemia (increased plasma Urea and Creatinine) Oliguria (low urine output <400 ml/day) Red blood cell casts (seen with urine analysis and microscopy) Pyuria (white blood cells or pus in the urine) Causes

Nephrotic syndrome

Along with obtaining a complete medical history, a series of biochemical tests are required in order to arrive at an accurate diagnosis that verifies the presence of the illness. In addition, imaging of the kidneys (for structure and presence of two kidneys) is sometimes carried out, and/or a biopsy of the kidneys. The first test will be a urinalysis to test for high levels of proteins, as a healthy subject excretes an insignificant amount of protein in their urine. The test will involve a 24-hour bedside urinary total protein estimation. The urine sample is tested for proteinuria (>3.5 g per 1.73 m2 per 24 hours). It is also examined for urinary casts, which are more a feature of active nephritis. Next a blood screen, comprehensive metabolic panel (CMP) will look for hypoalbuminemia: albumin levels of ≤2.5 g/dL (normal=3.5-5 g/dL). Then a Creatinine Clearance CCr test will evaluate kidney function particularly the glomerular filtration capacity. Creatinine formation is a result of

InternalMed_Harrison

Fever ˜38.3° C (101° F) and illness lasting ˜3 weeks and no known immunocompromised state History and physical examination Stop antibiotic treatment and glucocorticoids Obligatory investigations: ESR and CRP, hemoglobin, platelet count, leukocyte count and differential, electrolytes, creatinine, total protein, protein electrophoresis, alkaline phosphatase, AST, ALT, LDH, creatine kinase, antinuclear antibodies, rheumatoid factor, urinalysis, blood cultures (n=3), urine culture, chest x-ray, abdominal ultrasonography, and tuberculin skin test

Routine serologic tests in the differential diagnosis of the adult nephrotic syndrome.

From 1980 to 1985, we performed biopsies on 87 adults with nephrotic syndrome (NS). The patients were tested for whether serologic studies obtained routinely at biopsy added to clinical diagnostic accuracy. Using history, physical examination, complete blood cell count (CBC), chemistry panel, urinalysis, and urine creatinine and protein, four nephrologists each predicted whether the patient had primary NS (PNS) or secondary NS (SNS), and the most likely histopathologic entity. Six months later, each nephrologist used this information, with results of tests of sera for fluorescent antinuclear antibody (FANA), rheumatoid factor (RF), complement components, hepatitis B surface antigen (HBsAg), venereal disease research laboratory serology (VDRI), cryoglobulins and protein electrophoresis (SPEP), with an erythrocyte sedimentation rate (ESR) and protein electrophoresis of the urine (UPEP), to make identical predictions. Histopathology was established by renal biopsy. We analyzed the concordance between nephrologists' choices and biopsy results both before and after serologic tests were available with a kappa statistic. Preserology concordance was moderate (kappa = 0.52), and identical to postserology concordance (kappa = 0.51) for both PNS versus SNS and actual histopathology. Serologies were rarely abnormal without clinical suspicion. These results suggest routine serologic testing does not improve diagnostic accuracy in adult NS.

InternalMed_Harrison

PART 2 Cardinal Manifestations and Presentation of Diseases HEMATURIA Proteinuria (>500 mg/24 h), Dysmorphic RBCs or RBC casts Pyuria, WBC casts Urine culture Urine eosinophils Hemoglobin electrophoresis Urine cytology UA of family members 24 h urinary calcium/uric acid IVP +/Renal ultrasound As indicated: retrograde pyelography or arteriogram, or cyst aspiration Cystoscopy Urogenital biopsy and evaluation Renal CT scan Renal biopsy of mass/lesion Follow periodic urinalysis Renal biopsy FIguRE 61-2 Approach to the patient with hematuria. ANCA, antineutrophil cytoplasmic antibody; ASLO, antistreptolysin O; CT, computed tomography; GBM, glomerular basement membrane; IVP, intravenous pyelography; RBC, red blood cell; UA, urinalysis; VDRL, Venereal Disease Research Laboratory; WBC, white blood cell.

InternalMed_Harrison

FIguRE 61-3 Approach to the patient with proteinuria. Investigation of proteinuria is often initiated by a positive dipstick on routine urinalysis. Conventional dipsticks detect predominantly albumin and provide a semiquantitative assessment (trace, 1+, 2+, or 3+), which is influenced by urinary concentration as reflected by urine specific gravity (minimum, <1.005; maximum, 1.030). However, more exact determination of proteinuria should employ a spot morning protein/creatinine ratio (mg/g) or a 24-h urine collection (mg/24 h). FSGS, focal segmental glomerulosclerosis; RBC, red blood cell; UPEP, urine protein electrophoresis.

Cholesterol embolism

Tests for inflammation (C-reactive protein and the erythrocyte sedimentation rate) are typically elevated, and abnormal liver enzymes may be seen. If the kidneys are involved, tests of kidney function (such as urea and creatinine) are elevated. The complete blood count may show particularly high numbers of a type of white blood cell known as eosinophils (more than 0.5 billion per liter); this occurs in only 60-80% of cases, so normal eosinophil counts do not rule out the diagnosis. Examination of the urine may show red blood cells (occasionally in casts as seen under the microscope) and increased levels of protein; in a third of the cases with kidney involvement, eosinophils can also be detected in the urine. If vasculitis is suspected, complement levels may be determined as reduced levels are often encountered in vasculitis; complement is a group of proteins that forms part of the innate immune system. Complement levels are frequently reduced in cholesterol embolism, limiting the use

[Asymptomatic microhematuria].

Microscopic haematuria is an urinary finding more and more frequently observed in routine analysis in childhood; the diagnostic problems, most of which unresolved, are yet the principal questions of concern. We have studied 123 patients during five years from 1975 to 1980, and followed them for 1-8 years (mean 4 years). Our experience allowed us to consider "normal" or without remarkable pathologic significance a urinary finding less than or equal to 5.000 RBC/m' at the Addis count. Such findings were pointed out in 55 cases (44%); 27 patients (22%) had 5-10.000 RBC/m', 34 cases (27,6%) presented 10-50.000 RBC/m' and 7 cases (5,7%) had more then 50.000 RBC/m'. The familiar background, the clinical, biological and immunological data, the roentgenographic investigations and the renal biopsy carried out in the 4 groups of patients, led us to the following conclusions: 1) 26% of the 123 cases had a "unexplained;; microscopic haematuria with complete lack of anamnestic data, symptomatology and with normal biological findings. 2) in 65,8% of the cases it was possible to discover frequent upper respiratory tract infections (and allergy in 5,6% of them). 3) in 26% of the patients we discovered a previous or actual genito-urinary (10,5% and 15,5% respectively) infection: 9,4% of 96 urography demonstrated a variable degree of nephro-urological abnormalities. 4) 23 children (18,7%) was selected for renal biopsy, primarily by the hypocomplementemia and positive anti-DNA ab. test, and secondly by elevated degree of microhematuria. The histological and immunohistochemical studies demonstrated the presence of mesangial proliferation glomerulonephritis with IgG-IgA-C3 deposits in 7 cases (30% of the cases biopsied and 5,6% of the total), 69,6% of the cases had only minimal charges with negative immunofluorescence. 5) A mean follow-up of 4 years in two groups of patients (less than or greater than 6 years of age) has demonstrated that microscopic haematuria remains unchanged in 18-19% of both groups. A more marked improvement or normalization has been documented in the children more than 6 years aged (p less than 0,001) while a worsening has been observed in the children less than 6 years aged (p less than 0,005), with a statistically significant difference between the two groups considered.

Microhematuria

Microhematuria, also called microscopic hematuria (both usually abbreviated as MH), is a medical condition in which urine contains small amounts of blood; the blood quantity is too low to change the color of the urine (otherwise, it is known as gross hematuria). While not dangerous in itself, it may be a symptom of kidney disease, such as IgA nephropathy or Sickle cell trait, which should be monitored by a doctor. The American Urological Association (AUA) recommends a definition of microscopic hematuria as three or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens. Microhematuria is usually asymptomatic, and there are medical guidelines on how to handle asymptomatic microhematuria (AMH) so as to avoid problems such as overtreatment or misdiagnosis. See also Proteinuria Hematuria Myoglobinuria Hemoglobinuria References External links 2012 AUA Guidelines

[Rationalization of urine analysis while maintaining diagnostic accuracy (author's transl)].

Screening 720 morning urinary samples for WBC, RBC and protein by test-strip, the number of subsequent microscopic examinations of urinary sediment was reduced to about half, without missing any significant number of clinically significant findings (4.4%). On the other hand, a large number (21.3%) of cases with obviously false-negative sediment findings were revealed. These were largely due to lysis of WBC and RBC, as well as poorly standardized methods of examining urinary sediment. But they could also have been due to differences in subjective criteria employed by the technicians. Our results indicate that using test-strips for screening, clinical routine examination can be rationalized, taking about half the time needed for sediment examination, with more potentially significant findings being discovered than missed.

[Clinical and laboratory correspondence to outpatients with the extreme value of C-reactive protein].

It is the policy of Tenri Hospital to notify the patient promptly whenever an extreme laboratory data value is detected. We investigated the utility of forwarding clinical and laboratory correspondence to outpatients with extreme value of C-reactive protein (CRP). Sixty-eight outpatients with CRP levels more than 20 mg/dl detected during 1986 were studied. CRP was measured by turbidometric method, and a sample with CRP level more than 15 mg/dl was diluted with CRP negative serum (CRP level less than 0.2 mg/dl) and was reanalyzed. Fifty-two of 68 patients (76%) had infectious diseases as the causal disease of high CRP, and eight (12%) had other diseases. In the remaining (12%) the causes were unknown. In most patients the causal diseases were diagnosed within one or two days, but diagnosis required more than 4 days in those with acute pyelonephritis, meningitis, liver abscess or renal abscess, as these diseases were diagnosed after the examination of urine or cerebrospinal fluid, or after ultrasonography. Thirty-seven of 58 patients (64%) who had appointments with their physician on the day of the laboratory examination were admitted the same day, and two of 10 patients (20%) who had appointments on the following day were admitted on that day. Seventeen of 25 patients (68%) with urea-N levels more than 30 mg/dl, cholinesterase levels less than 0.7 delta pH and albumin levels less than 3.5 g/dl required more than 15 days to recover, while 29 of 32 patients (91%) with only 2 or fewer of these laboratory values required less than 14 days. The prompt notification of extreme CRP value is an important aspect of medical care. The examination of urine and cerebrospinal fluid and ultrasonography are necessary screening techniques accompanying examination of blood and plain chest X-ray. Urea-N, cholinesterase and albumin values should be determined at the same time as CRP value to assess prognosis.

Urine test strip

Urinary sediment During routine screening, if a positive test for leukocytes, blood, protein, nitrite, and a pH greater than 7 is identified, the urine sediment be microscopically analysed to further pinpoint a diagnosis. Automated analysers Automatic analysis of urine test strips using automated urine test strip analysers is a well-established practice in modern-day urinalysis. They can measure calcium, blood, glucose, bilirubin, urobilinogen, ketones, leukocytes, creatinine, microalbumin, pH, ascorbic acid and protein. References Further reading Compendium Urinalysis: Urinalysis with Test Strips. Dr E F Hohenberger, Dr H Kimling (2002)http://www.diavant.com/diavant/servlet/MDBOutput?fileId=1392 Urinalysis Strips Instructions Urine tests

[Critical study of microscopic hematuria disclosed by screening tests].

Asymptomatic microscopic haematuria detected by dipstick in 0.28 p. 100 of 95,200 men was confirmed in only 0.11 p. 100. These results lead to the study of 272 cases to determine the value of dipsticks as a screening test and the benefits of complementary investigations to exclude symptomless diseases. Microscopic haematuria was confirmed in 65 p. 100 but results of other tests reduce the false positive screening results to 25.3 p. 100. Addis counting of at least 5,000 RBC/min is preferable to RBC count/ml which is dilution dependent. 77 p. 100 of microscopic haematuria are intermittent and can only be diagnosed by repeated Addis counts. In the absence of confirmed haematuria, only investigations to exclude proteinuria and urinary infections are justified.

Microalbuminuria -- Evaluation

In order to determine the cause of albuminuria as the underlying glomerular disease, the following should be done: Urine microscopy – Presence of dysmorphic red blood cells/casts 24-hour urine collection for the quantification of albumin excretion Serum creatinine, blood glucose, albumin, and cholesterol Autoantibody panel - If indicated by the clinical picture, test for antinuclear antibody (ANA), antistreptolysin O titers, anti-DNA antibodies, antineutrophil cytoplasmic antibodies (ANCA), cryoglobulins, anti-glomerular basement membrane (anti-GBM) antibodies, and complement levels (C3 and C4) Imaging studies in albuminuria may include the following: Renal ultrasonography – To establish glomerular disease as the cause of microalbuminuria, it is imperative to look at the echogenicity and size of the kidneys [18] Chest X-ray or computed tomography (CT) scan – If guided by the clinical picture

Urine test strip

Blood Blood may be present in the urine either in the form of intact red blood cells (hematuria) or as the product of red blood cell destruction, hemoglobin (hemoglobinuria). Blood present in large quantities can be detected visually. Hematuria produces cloudy red urine, and hemoglobinuria appears as a clear red specimen. Any amount of blood greater than five cells per microliter of urine is considered clinically significant; visual examination cannot be relied upon to detect the presence of blood. Microscopic examination of the urinary sediment shows intact red blood cells, but free hemoglobin produced either by hemolytic disorders or lysis of red blood cells is not detected. Therefore, chemical tests for hemoglobin provide the most accurate mean for determining the presence of blood. Once blood has been detected, the microscopic examination can be used to differentiate between hematuria and hemoglobinuria.

Laboratory and imaging studies used by French rheumatologists to determine the cause of recent onset polyarthritis without extra-articular manifestations.

The cause of recent onset polyarthritis can be difficult to identify. To determine which laboratory and imaging studies French rheumatologists recommend, not taking cost into account, for the diagnosis of recent onset polyarthritis without extra-articular manifestations. From the list of the French Society for Rheumatology, a random sample of 210 rheumatologists was selected, who were asked to complete a questionnaire on the laboratory and imaging studies they would recommend in two fictional cases of recent onset polyarthritis (possible rheumatoid arthritis (RA)-case 1 and probable RA-case 2). In case 1, the following were recommended by over 75% of respondents: hand radiographs, rheumatoid factors (RFs), and antinuclear antibodies (ANA) (92%, 98%, and 98%, respectively). 50-74% of respondents recommended radiographs of the feet, knees, and chest (50%, 57%, and 66%, respectively); blood cell counts, erythrocyte sedimentation rate (ESR), serum assays of C reactive protein (CRP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (65%, 74%, 67%, and 62%, respectively). 25-49% recommended determination of creatinine and proteinuria, HLA-B27, antikeratin antibody, radiographs of the pelvis, and synovial fluid analysis. Several investigations were recommended less often in case 2 than in case 1. Nevertheless, some laboratory and imaging studies (radiographs of hand, feet, knees, chest x rays, blood cell counts, ANA, RF, antikeratin antibody, CRP, ESR, creatinine, AST and ALT, proteinuria, and joint aspiration) were recommended by more than 25% of respondents in both cases. Wide variations were found among rheumatologists, indicating a need for standardisation. Some laboratory and imaging studies are recommended by at least 25% of respondents in recent onset polyarthritis with or without clues suggesting RA. In contrast, many tests were considered useful by fewer than 25% of the respondents in both cases.