Acute tubular necrosis following interferon-based therapy for hepatitis C: case study with literature review.

BACKGROUND/AIMS: Interferon treatment of malignant or viral diseases can be accompanied by various side-effects including nephro-toxicity. METHODS: We report on a 68-year-old Caucasian male who received dual therapy with pegylated interferon 2a plus ribavirin for chronic hepatitis C. RESULTS: After three months of antiviral therapy, the patient developed acute kidney failure (serum creatinine up to 6 mg/dL) with mild proteinuria (500 mg daily) and haematuria. Immediate immunosuppressive therapy with high-dose intravenous steroids did not improve kidney function. Kidney biopsy was consistent with acute tubular necrosis without glomerular abnormalities. He started long-term peritoneal dialysis (four regular exchanges) to provide both dialysis adequacy and ascites removal. Kidney function gradually improved over the following months (serum creatinine around 2 mg/dL) and peritoneal dialysis was continued with two exchanges daily. The temporal relationship between the administration of the drug and the occurrence of nephro-toxicity, and the absence of other obvious reasons for acute tubular necrosis support a causative role for pegylated interferon; benefit on kidney disease was noted after withdrawal of antiviral agents. An extensive review of the literature on acute tubular necrosis associated with interferon-based therapy, based on in vitro data and earlier case-reports, has been made. The proposed pathogenic mechanisms are reviewed. CONCLUSIONS: Our case emphasizes the importance of monitoring renal function during treatment of chronic hepatitis C with antiviral combination therapy as treatment may precipitate kidney damage at tubular level.

[The classics of Italian nephrology: ''Hormones in renal physiology and renal pathology'' by Silvano Lamperi (1922-2008) e Rodolfo Cheli (1928-1997)]. / I Classici della Nefrologia Italiana. ''Gli ormoni nella fisiologia e nella patologia del rene'' di Silvano Lamperi (1922-2008) e Rodolfo Cheli (1928-1997).

This monograph, published in 1955, describes the effects that cortisone, desoxycorticosterone, adrenocorticotropic hormone, growth hormone, and testosterone have on renal function, renal metabolism and renal enzymatic activity. The two main chapters of the book describe the experimental results obtained by the authors with the administration of the above-mentioned hormones to rats in terms of renal morphology and function both in basal conditions and after the injection of nephroptoxic substances. Interestingly, the effects on function were evaluated by the measurement of the consumption of oxygen by kidney sections incubated with hormones in different experimental conditions. The results demonstrated that both cortisone and adrenocorticosterone could have a protective effect on kidney damage, which could be used for clinical purposes. Today, the monograph by Lamperi and Cheli is interesting because it shows that advanced experimental research was carried out in Italy in the early 1950s. Moreover, it represents an early attempt to the application of experimental results to the clinic.

A virtuous diagnostic and therapeutic roadmap triggered by a motivated and skilful urinary sediment examination.

In this paper we describe how an accurate urinary sediment examination, which revealed the presence of a severe 2,8-dihydroxyadenine crystalluria, opened the way to an articulate and successful diagnostic and therapeutic roadmap for a rare and potentially severe renal disease.

[The classics of Italian nephrology. 'Functional semiology of the kidney' by Giovanni Gigli (1913-1988) and Sergio Giovannetti (1924-2000)]. / I Classici della Nefrologia Italiana. ''Semeiologia funzionale del rene'' di Giovanni Gigli (1913-1988) e Sergio Giovannetti (1924-2000).

The monograph Semeiologia funzionale del rene (Functional semiology of the kidney) by Giovanni Gigli (1913-1988) and Sergio Giovanetti (1924-2000), published in 1953, was the first systematic survey on the subject to appear in Italy. Besides the classical renal function tests (urinalysis, BUN measurement, urea clearance), the book recounts the many new techniques that were introduced into clinical practice in that period as a result of the great advances in the field of renal physiology (e.g., glomerular filtration rate, renal plasma and blood flow, tubular water reabsorption, maximum tubular excretion and reabsorption capacity, filtration fraction). In addition, it describes the utility and pitfalls of such tests in a wide spectrum of kidney diseases, but especially in different types of glomerulonephritis, of which the two authors had collected a personal cohort of 48 patients. Today, the monograph by Gigli and Giovannetti shows the difficulties and uncertainties encountered in the evaluation of kidney diseases in a period in which renal biopsy was yet to become the widely used technique it is today.

[The Classics of Italian Nephrology: ''The physiopathological basis for the nosography and the classification of bilateral kidney diseases'' by Pio Bastai (1888-1975) and Massimo Crepet (1911-1994)]. / I Classici della Nefrologia Italiana. ''I fondamenti fisiopatologici per la nosografia e la classificazione delle malattie renali bilaterali'' di Pio Bastai (1888-1975) e Massimo Crepet (1911-1994).

The paper ''I fondamenti fisiopatologici per la nosografia e la classificazione delle malattie renali bilaterali'' (The physiopathological basis for the nosography and the classification of bilateral kidney diseases'') by Pio Bastai (1888-1975) and Massimo Crepet (1911-1994) was presented at the 54th Congress of the Italian Society of Internal Medicine, which was held in October 1953 in Rome. In the report, the authors proposed their own classification of renal diseases based on a ''physopathological'' criterion and different from the classifications proposed by other authors of the period. According to Bastai and Crepet, renal diseases could be classified into arteriolopathies (either acute or chronic), capillary diseases (glomerulonephritides, including inflammatory and noninflammatory forms), renal diseases due to circulatory failure, nephropathies due to toxic substances, interstitial nephropathies, and idiopathic nephropathies. Of particular interest today is the part of the paper on the nosography of the so-called ''genuine glomerulonephrosis'' which, at variance with the view of the leading clinicians at the time, was placed among the inflammatory glomerulonephritides. In addition, the authors expressed their uncertainty about the existence of primary chronic interstitial nephropathies. Today, the paper by Bastai and Crepet shows how difficult it was to propose a classification of renal diseases in a period when the use of renal biopsy was still in its infancy.

Microscopic examination of urine sediment: Phase contrast versus bright field.

BACKGROUND: Today, phase contrast microscopy (PCM) is the recommended technique for manual urinary sediment (U-sed) examination. In fact, compared to bright field microscopy (BFM), it allows a better identification of most U-sed particles. METHODS: The main contributions, both as original papers in medical journals and as monographs on PCM applied to U-sed examination, published in the period 1950-1982 (which was chosen because it includes the results of the most important investigations on the subject) were identified and analysed. Moreover, a brief analysis on the use of PCM in U-sed examination today was carried out. RESULTS: After the discovery of PCM by the Dutch physicist Frits Zernike in the 1930s, several contributions were published, most of which are forgotten today. All of them demonstrated the advantages of PCM over BFM in identifying the U-sed particles, especially casts, renal tubular epithelial cells, atypical urothelial cells associated with urothelial carcinoma, and erythrocytes (which for the 1st time were classified as dysmorphic - of glomerular origin - and isomorphic - of non glomerular origin). The analysis of six recent monographs on U-sed or urinalysis, written in English and with an international distribution, demonstrated that only in two of them the U-sed particles were mostly shown by PCM. CONCLUSION: Several papers and monographs, published since the early 1950s, have demonstrated the advantages of PCM over BFM for U-sed examination. In spite of this, PCM is not as widely used as it should be.

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.

BACKGROUND: Crystals 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). METHODS: Reports 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. RESULTS: DLcr 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. CONCLUSIONS: This paper confirms the possible presence in the urine of DLcr. However, further cases are needed to clarify their frequency, clinical meaning, and composition.

[Historical Archives of Italian Nephrology. Gabriele Monasterio (1903-1972) and the School of Pisa]. / Archivi storici della Nefrologia Italiana: Gabriele Monasterio (1903-1972) e la Scuola di Pisa.

Gabriele Monasterio (1903-1972), a clinician with numerous medical interests, contributed remarkably to the development of the Italian nephrology of his time. His main scientific contributions were: - Investigation of the causes of normoglycaemic glycosuria. Of this condition he collected, from 1939 on, a large series of patients whom he also investigated - for the first time in the world - with renal biopsy and - thanks to a collaboration with Jean Oliver - the microdissection of the nephron. - Introduction, in the early 1960s, of a low protein diet for the patients with chronic renal failure. This, thanks to the stud-ies published by Monasterio co-workers Quirino Maggiore and Sergio Giovannetti, was largely used in Italy and abroad. - Classification of the nephropathies. This was described in the monograph Le Nefropatie Mediche (1954 and 1970), which had a large impact and today represents a classic of the Italian nephrological literature. Monasterio served remarkably the Italian Society of Nephrology: in 1957 as a member of the founding committee; from 1959 to 1962 and from 1964 to 1968 as President; in 1958, 1962, and 1964 as organizer of the National Congress; from 1962 to his death as the Editor-in-Chief of the official journal of the Society, Minerva Nefrologica. Finally, Monasterio was also a member of the first council of the International Society of Nephrology.

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

BACKGROUND: Urinary 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. METHODS: Included 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. RESULTS: A/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. CONCLUSIONS: At 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.

Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients.

Histological features and data on the natural history after 1 to 45 years (mean 6.56 +/- 8.55) of total apparent duration and 1 to 13 years (mean 3.48 +/- 5.04) of post-biopsy follow-up, are reported in 374 patients (mean age, 33.9 +/- 11.9 yrs) with idiopathic mesangial IgA nephropathy, who presented with a history of macroscopic hematuria (56%), recurrent in two-thirds of the patients, or with persistent microscopic hematuria and no previous episodes of gross hematuria (44%). Mesangial cell proliferation ranged from minimal to diffuse. Associated varying degrees of extracapillary proliferation, segmental and global glomerular sclerosis, tubulo-interstitial damage and arteriolar hyalinosis usually correlated with each other and with the extent of mesangial proliferation (P less than 0.05). The actuarial curve of progression to renal death showed a 75% survival after 20 years from apparent onset. Progression to renal failure was more rapid in patients with: an older age at onset (P = 0.0582); male sex (P = 0.0730); no history of recurrent gross hematuria (P = 0.0406); high blood pressure (P = 0.0011); more marked global (P = 0.0007) and segmental (P = 0.0026) glomerular sclerosis; more severe interstitial sclerosis (P = 0.0147); more diffuse and global mesangial proliferation (P = 0.0820); mesangio-parietal pattern at immunofluorescence (P = 0.0778). However, all these parameters showed a poor predictive value if applied to any single patient.

Light chain deposition disease of the kidney. Morphological aspects in 24 patients.

Renal biopsies and autopsy specimens of 23 patients with light chain deposition disease (LCDD) and one with only heavy chain deposits, were studied by light (LM) and electron microscopy (EM) as well as immunohistology (IH). Thirteen patients had multiple myeloma; 1 had lymphoma, and 1 chronic myeloid leukaemia with polycythaemia vera. In nine patients, no lymphoproliferative disease was identified. The LM lesions most suggestive of LCDD, nodular glomerulosclerosis (NS) and thickening and wrinkling of the tubular basement membranes (TBM), were present in only ten and 13 patients, respectively. In five of seven specimens without NS or TBM thickening by LM, EM was negative, indicating a limited value of EM in confirming the diagnosis. Renal amyloidosis was not identified, but in one patient amyloid in the heart and tongue was seen at autopsy. One patient had both granular and extensive glomerular non-amyloid fibrillary deposits. In two patients myeloma casts were identified. Twenty-one patients showed renal LC immune reactivity, 1 had both alpha heavy and lambda LC, 1 had only detectable gamma heavy chain. One biopsy was negative by IH, but had characteristic electron dense deposits. In six patients with immune reactivity to LC, no electron dense deposits could be identified by EM. This study emphasizes the spectrum of renal changes by LM and EM in LCDD, the frequent lack of consistency between deposits detected by IH and EM and the difficulty in coming to a definite diagnosis without LM, EM and IH. The results of this study and examination of the literature indicates that extensive morphological changes are more often present in kappa than in lambda LCDD.

External quality assessment of urine analysis in Europe. Results of a round table discussion during the symposium 'From uroscopy to molecular analysis', Seeon, Germany, September 18-20, 1999.

Interlaboratory surveys on urine quantities have only recently been introduced in several European countries. Representatives of 10 European countries exchanged their experiences during an international urinalysis meeting held in September 1999. Although still not mandatory in most areas, more than 5000 laboratories participated in external quality assessment programs in the countries represented. Qualitative (test strips and microscopic morphology) as well as quantitative chemical and immunochemical quantities were included. The maximal allowable deviations are reported as well as methods used to determine target values. Consensus scales up to reference methods were applied. The participants agreed that quality criteria need to be defined separate from those already existing for plasma/serum analytes. Besides higher biological variables and different medical needs, less standardisation of methods to quantify urine constituents was observed as a major cause of higher interlaboratory differences.

Towards European urinalysis guidelines. Introduction of a project under European Confederation of Laboratory Medicine.

Improved standardized performance is needed because urinalysis continues to be one of the most frequently requested laboratory tests. Since 1997, the European Confederation of Laboratory Medicine (ECLM) has been supporting an interdisciplinary project aiming to produce European urinalysis guidelines. More than seventy clinical chemists, microbiologists and ward-based clinicians, as well as representatives of manufacturers are taking part. These guidelines aim to improve the quality and consistency of chemical urinalysis, particle counting and bacterial culture by suggesting optimal investigative processes that could be applied in Europe. The approach is based on medical needs for urinalysis. The importance of the pre-analytical stage for total quality is stressed by detailed illustrative advice for specimen collection. Attention is also given to emerging automated technology. For cost containment reasons, both optimum (ideal) procedures and minimum analytical approaches are suggested. Since urinalysis mostly lacks genuine reference methods (primary reference measurement procedures; Level 4), a novel classification of the methods is proposed: comparison measurement procedures (Level 3), quantitative routine procedures (Level 2), and ordinal scale examinations (Level 1). Stepwise strategies are suggested to save costs, applying different rules for general and specific patient populations. New analytical quality specifications have been created. After a consultation period, the final written text will be published in full as a separate document.

Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial.

Corticosteroids have had variable success in IgA nephropathy (IgAN). Our previous trial with a six-month course of steroids in IgAN patients showed they were effective in reducing the risk of renal function deterioration and proteinuria, but this effect seemed to decrease in the long term. This new randomised trial was designed to prospectively evaluate whether adding low-dose azathioprine to steroids improves long-term renal survival in adult biopsy-proven IgAN patients with proteinuria > or = 1 g/24 h and plasma creatinine < or = 2.0 mg/dl. The patients will be treated with steroids (methylprednisolone 1 g i.v. for three consecutive days at months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for six months) plus azathioprine 1.5 mg/kg/day for six months or steroids alone with the same schedule. Altogether a minimum of 346 patients should be enrolled within a four-year recruitment period. The planned duration of follow-up is five years.

Renal disease and patient survival in light chain deposition disease.

We evaluated retrospectively the presenting clinical features, response to treatment and clinical course of 19 patients with LCDD, 11 of whom had multiple myeloma. At presentation, renal insufficiency was present in 18 patients and proteinuria in 16. Renal biopsy revealed typical LCDD in 16 patients, while in the remaining three LCDD was associated with other abnormal tissue deposits. Extrarenal signs were observed in 12 patients (63%), with the liver, heart and peripheral nerves being the most frequently involved organs. After diagnosis, 18 patients underwent therapy: 2 received steroids alone and 16 were treated with steroids and cytotoxic drugs; 7 patients also underwent plasma exchange. At the end of the first month of treatment renal function improved in 5 patients, worsened in 5 and remained unchanged in 8. All but 3 of the patients continued treatment beyond the first month: 7 patients developed end-stage renal disease, 5 an improvement and 4 a worsening in renal function. No effect on proteinuria was observed. Extrarenal symptoms developed in 4 previously unaffected patients and in 3 others they extended to more organs. Sixteen patients died: 12 during the first year of the follow-up, and 4 at 21st, 34th, 37th and 82nd month of observation. Five patients died from neoplastic cachexia, 4 from hypokinetic cardiopathy, 3 from hemorrhagic complications, 2 from pneumonia and one from unknown cause. Mean patient survival after presentation was 18.1 +/- 20.7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term outcome of Schönlein-Henoch nephritis in the adult.

Sixteen adult patients with Schönlein-Henoch nephritis, selected by strict inclusion criteria, were studied retrospectively. At the time of discovery of the nephropathy, 11 patients had normal plasma creatinine and 5 other patients had renal insufficiency. All patients had renal biopsies, which were studied by both light and immunofluorescence microscopy. After a mean follow-up of 90.5 +/- 59.1 months (range 16-261), 3 patients were in chronic dialysis (18.7%), 8 other patients had renal function deterioration (50%), with creatinine clearance ranging from 31 to 60 ml/min. Four other patients had mild urinary abnormalities with normal plasma creatinine (25%) and only 1 patient was in complete clinical remission (6%). No clinical features at onset were predictive for the clinical outcome of the disease, while in the biopsies the percentage of crescents was higher in patients who developed renal insufficiency. High IgA serum levels were correlated (p = 0.0242) with a favorable course. It is concluded that Schönlein-Henoch nephritis of the adult carries a high long-term risk of renal dysfunction.

Comparison of immunofluorescent findings in kidney after snap-freezing and formalin fixation.

Two types of tissue preparation for immunofluorescent staining were compared with sections of the same kidney. In one, formalin-fixed paraffin-embedded kidney sections were incubated with pronase (IF-PRON). The optimal pronase exposure for bright, specific IF and a mild background IF, suitable for the whole set of antisera was determined (pronase 0.75 g/l of Tris buffer for 60 min) and this was used for the subsequent steps of the study. Snap-frozen sections were also stained (IF-FROZ). Positive and negative cases, IF intensity, distribution and location in IgA nephropathy, membranous nephropathy, proliferative lupus nephritis were compared by the 2 methods. The main antigens for each disease were adequately revealed by IF-PRON, so that a correct diagnosis was possible in all cases. IF-PRON was also applied to sections before and after prolonged storage of blocks in the files, to see whether or not retrospective analysis is possible. Only minor differences were found between the 2 series of sections. Finally, the exposure of the sections to the continuous fluorescent light showed that IF fading was less in fixed sections. We conclude that IF-PRON is a reliable method for renal pathology with some advantages over the IF-FROZ.

Late recurrence of systemic vasculitis after kidney transplantation involving the kidney allograft.

A patient is described in whom a recurrence of vasculitis was observed in the kidney allograft six years after transplantation and one year after withdrawal of corticosteroid therapy. This case shows that systemic vasculitis may recur at any time after transplantation which implies a continuous and careful monitoring of these patients.