Giuseppe Garigali

Urinary Sediment Findings in Acute Interstitial Nephritis

RESEARCH LETTERS Urinary Sediment Findings in Acute Interstitial Nephritis To the Editor: Acute interstitial nephritis (AIN) is a condition characterized by acute kidney injury associated with acute cellular infiltrate of the renal interstitium due to various causes. Published data for urinary sediment findings in AIN are few. In this case series, we describe detailed findings observed in 21 patients with biopsy-proven AIN due to different causes. We reviewed all reports of biopsies performed on native kidneys at our institution during a 14-year period (January 1, 1997, to February 1, 2011) and identified AIN cases. All patients with AIN were considered for inclusion. All microscopic slides arising from these kidney biopsies were reviewed by 2 of us for the presence or absence of interstitial cellular infiltrate, tubulitis, tubular necrosis, tubular basement membrane gaps, interstitial red blood cell (RBC) extravasation, RBCs, and intratubular RBC casts. Of 839 kidney biopsies, 23 (2.7%) were found to have AIN in the absence of significant glomerular lesions. We included 21 patients (Table 1), having excluded one because of bacteria (2 ) in the urinary sediment and another for focal glomerular immunoglobulin A and C3 by immunofluorescence (which was negative at the glomerular level in all other cases).

Advances in Urine Microscopy.

Urine microscopy is an important tool for the diagnosis and management of several conditions affecting the kidneys and urinary tract. In this review, we describe the automated instruments, based either on flow cytometry or digitized microscopy, that are currently in use in large clinical laboratories. These tools allow the examination of large numbers of samples in short periods. We also discuss manual urinary microscopy commonly performed by nephrologists, which we encourage. After discussing the advantages of phase contrast microscopy over bright field microscopy, we describe the advancements of urine microscopy in various clinical conditions. These include persistent isolated microscopic hematuria (which can be classified as glomerular or nonglomerular on the basis of urinary erythrocyte morphology), drug- and toxin-related cystalluria (which can be a clue for the diagnosis of acute kidney injury associated with intrarenal crystal precipitation), and some inherited conditions (eg, adenine phosphoribosyltransferase deficiency, which is associated with 2,8-dihydroxyadenine crystalluria, and Fabry disease, which is characterized by unique urinary lamellated fatty particles). Finally, we describe the utility of identifying decoy cells and atypical malignant cells, which can be easily done with phase contrast microscopy in unfixed samples.

An Italian external quality assessment (EQA) program on urinary sediment.

BACKGROUNDnEQA programs on urinary sediment are rare. We describe an EQA Italian program which started in 2001 and involves today more than 300 laboratories.nnnMETHODSnThe program, which started with a questionnaire about the methodological aspects on urinary sediment, includes today four surveys per year. These ask the participants the identification and clinical associations of urinary sediment particles shown by colour images (surveys 1 and 3) and the diagnosis of clinical cases presented by both images and a short clinical history (surveys 2 and 4). The results of each survey are then scored and commented.nnnRESULTSnQuestionnaire (participants = 287): most methodological aspects were not dealt with properly.nnnIDENTIFICATIONncells, lipids, casts and some contaminants were poorly known. However, when 27 particles were presented for the second time and 16 particles for the third time, the correct identification rate for most of them increased significantly. Clinical associations (No presented = 16): a correct answer was indicated by > or = 84% of participants for all particles but one. Clinical cases (No presented=4): lowest correct identification for urine contamination from genital secretion (77.3%), highest for ureteric stone (94.4%).nnnCONCLUSIONSnOur program shows that EQA programs are both useful and needed.

Atypical/malignant urothelial cells in routine urinary sediment: Worth knowing and reporting

BACKGROUNDnUrinary cytology (Ucytol), which is performed in pathology laboratories on fixed and stained samples, represents the gold standard for the identification of atypical/malignant urothelial cells (A/MUC) due to urothelial carcinoma. In this paper we describe three patients in whom A/MUC, due to a bladder carcinoma, were identified with conventional urine sediment (Used) examination on unfixed and unstained samples.nnnMETHODSnIncluded are urine samples prepared with conventional and standardized techniques as currently used in general clinical laboratories. Samples were examined with phase contrast microscopy. A/MUC were identified according to the criteria currently used for Ucytol.nnnRESULTSnA/MUC (i.e., cells with unusual and pleomorphic size and shape, increased nuclear/cytoplasmic ratio, increased number of nuclei, irregular nuclear borders and irregular chromatin patterns, either isolated or in clusters) were identified in the urine of three patients, all of whom were found to have bladder carcinoma by cystoscopy.nnnCONCLUSIONSnAt variance with the common and widespread view, A/MUC can also be identified with conventional Used examination, even though Ucytol still represents the gold standard method.

Waxy casts in the urinary sediment of patients with different types of glomerular diseases: Results of a prospective study☆

BACKGROUNDnCasts are well known components of the urinary sediment. For most casts, the clinical associations are known and demonstrated, while for waxy casts they are totally unknown.nnnMETHODSnProspective study for the search and count of waxy casts in the urinary sediment of patients with different types of glomerular diseases.nnnRESULTSnWaxy casts were found in 39 out of 287 patients (13.6%), mostly in low number (1 to 9 out of 100 casts evaluated/sample). They were frequent in postinfectious glomerulonephritis and renal amyloidosis (5/9 patients, 44.5%, p=0.02 for each condition), while they were rare in membranous nephropathy (4/67 patients, 6.0%, 0.04) and absent in focal segmental glomerulosclerosis (0/23 patients, p=0.05). Waxy casts were associated significantly with higher serum creatinine levels (p<0.0001), with the presence of >1 leukocyte/HPF, granular casts and leukocytic casts (p=0.001 to 0.008) and with higher numbers of erythrocytes, leukocytes, renal tubular epithelial cells, granular casts, epithelial casts, and leukocytic casts (p<0.0001 to=0.03).nnnCONCLUSIONSnWaxy casts are uncommon and few in patients with glomerular diseases and are associated with impaired renal function and with several other structures of the urinary sediment.

Adenine Phosphoribosyltransferase Deficiency: An Underdiagnosed Cause of Lithiasis and Renal Failure

We describe an infant affected by adenine phosphoribosyltransferase (APRT) deficiency diagnosed at 18 months of age with a de novo mutation that has not been previously reported. APRT deficiency is a rare defect of uric acid catabolism that leads to the accumulation of 2,8 dihydroxyadenine (2,8-DHA), a highly insoluble substance excreted by the kidneys that may precipitate in urine and form stones. The child suffered from renal colic due to a stone found in the peno-scrotal junction of the bulbar urethra. Stone spectrophotometric analysis allowed us to diagnose the disease and start kidney-saving therapy in order to avoid irreversible chronic kidney damage. APRT deficiency should always be considered in the differential diagnosis of pediatric urolithiasis.

How to identify sulfamethoxazole crystals in the urine.

In this paper we describe a patient whose urine, examined in blind conditions, contained hexagonal crystals made of Nacetylsulfamethoxazole hydrochloride (SMX), which is the main component, together with trimethoprim, of the largely used antimicrobial agent co-trimoxazole. On July 15th 2014, a 50-year-old man of Moroccan origin was evaluated for a periodical check-up in the outpatient clinic for kidney transplant recipients at Ospedale Maggiore Policlinico of Milano, Italy. On May 15th 2014, the patient had been submitted to a cadaveric kidney transplant, for end-stage renal disease caused by a pANCA+ systemic vasculitis. The daily therapy, which was unknown to the authors of the present paper at the time of urinary sediment examination, included: prednisone 10 mg, tacrolimus 4 + 3 mg, mycophenolate mofetil 1 g bid, omeprazole 20 mg, and co-trimoxazole (= sulfamethoxazole 800 mg + trimethoprim 160 mg) 1 tablet on an alternate day schedule, to prevent Pneumocistis jirovecii infection, which is common in the first months after kidney transplant due to immunosuppressive treatment. However, from July 10th, when the patient underwent a ureteric stent removal, the dose of co-trimoxazole had been increased to 1 tablet/day for 5 consecutive days, up to July 15th. The laboratory workup showed: a stable serum creatinine of 1.7 mg/dL (0.5–1.20) (eGFR by MDRD equation 46 mL/min/1.73 m), BUN 35.9 mg/dL (7–23.3), uric acid 6.8 mg/dL (2.4–7.0), total proteins 66 g/L (66–87), and albumin 42.8 g/L (34–48). ANCA test was negative for both proteinase 3 and myeloperoxidase. Blood glucose, electrolytes, blood cell count, liver enzymes and bilirubinwere all normal. Urinalysis by reagent strip: pH 5.0, relative density 1.030, glucose, hemoglobin, albumin, leukocyte esterase and nitrites negative. Urine sediment, examined by phase contrast microscopy: hyaline and hyaline-granular casts, N1/low power field (160×), monohydrate calcium-oxalate crystals (1–3/high power field, at 400×) and hexagonal crystals, 1 to 3/high power field. By phase contrast, the hexagons appeared as plates of variable size, either heaped one upon another or individual thin plates with a smooth surface, which could have easily been identified as cystine. However, by polarized light, the largest and heaped hexagonal crystals were strongly birefringent and polychromatic (Fig. 1, left), a fact which was in sharp contrast with cystine, while the individual thin hexagons were either no birefringent or displayed a pale to shining white birefringence, as cystine crystals usually do (Fig. 1, right).

Very unusual “needle- and pencil-like” uric acid crystals in the urine unmasked by infrared spectroscopy investigation

In this paper we describe a case with very unusual needle- and pencil-like crystals, partly similar to those reported by other investigators, who considered them as due to uric acid. Quite importantly, infrared spectroscopy investigation which, to our knowledge, we have been the first to perform on this type of crystals, confirmed their nature as uric acid structures. This case demonstrates that the planet of urinary crystals still has several unknown facets and still deserves exploration.

The different ways to obtain digital images of urine microscopy findings: Their advantages and limitations

We describe three ways to take digital images of urine sediment findings. Way 1 encompasses a digital camera permanently mounted on the microscope and connected with a computer equipped with a proprietary software to acquire, process and store the images. Way 2 is based on the use of inexpensive compact digital cameras, held by hands - or mounted on a tripod - close to one eyepiece of the microscope. Way 3 is based on the use of smartphones, held by hands close to one eyepiece of the microscope or connected to the microscope by an adapter. The procedures, advantages and limitations of each way are reported.

“Daisy-like” crystals: A rare and unknown type of urinary crystal

BACKGROUNDnCrystals are well known structures of urinary sediment, most of which are identified by the combined knowledge of crystal morphology, birefringence features at polarized light, and urine pH. In this paper, we report on a cohort of subjects whose urine contained a very rare type of crystal, which we first described in 2004 and which, based on its peculiar morphology, we define as daisy-like crystal (DLcr).nnnMETHODSnReports on DLcr were spontaneously sent to our laboratory over a 10.5-year period by different laboratory professionals and by one veterinary clinician who, in their everyday work, had come across DLcr. After the examination of DLcr images submitted, a number of other information were requested and partly obtained.nnnRESULTSnDLcr were found in 9 human beings in 7 different laboratories, located in 4 countries (Italy, Belgium, Croatia, France). DLcr were found mostly in female (8/9), at all ages (3.5 to 93years), mostly in alkaline urine (pH6.0 to 7.5), at variable specific gravity values (1.010 to 1.030), either as isolated particles (2/8) or in association with other crystals (5/8) and/or leucocytes or bacteria (3/8). In addition, DLcr were found in the urine of a 1-year-old dog, examined in a veterinary clinic of Czech Republic. In 3 cases, DLcr were identified by manual microscopy, while in 7 cases by automated urine sediment analyzers.nnnCONCLUSIONSnThis paper confirms the possible presence in the urine of DLcr. However, further cases are needed to clarify their frequency, clinical meaning, and composition.