Non-neoplastic Renal Diseases Research Articles

CAIX Immunostaining in Non-neoplastic Renal Diseases.

Carbonic anhydrase 9 (CAIX) is a transmembrane metalloenzyme that regulates cellular adhesion, proliferation, and intra/extracellular pH. It is expressed primarily through a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism. Its over-expression is closely related to somatic mutations in the Von Hippel-Lindau (VHL) gene. Studies have shown that it is over-expressed in renal cell carcinoma. In this study, we aimed to assess the value of CAIX immunostaining as an ancillary diagnostic tool in renal malignancies and medical renal diseases. Slides of kidney tumors and medical kidney diseases were selected to evaluate CAIX expression. Intensity and staining patterns of CAIX were independently assessed by two pathologists. Our results showed strong and diffuse box-like membranous staining pattern in the majority of the clear cell renal cell carcinoma (ccRCC) cases (47/59 cases; 94%). A strong, diffuse cup-shaped staining pattern was observed in clear cell papillary RCC. Variable positivity was observed in other RCC (renal cell carcinoma) subtypes. In non-neoplastic renal conditions, the majority of the cases were negative for CAIX, and only a few cases demonstrated patchy non-specific staining. Of note, a single case of transplanted kidney biopsy taken because of delayed graft function showed a focal area of dilated tubules lined by cells with clear cytoplasm and enlarged nuclei with prominent nucleoli. This area showed diffuse membranous staining for CAIX. Two cases of end-stage renal disease showed a focal circumferential membranous staining pattern for CAIX in dilated tubules. The CAIX immunoreactivity observed in these three cases could be indicative of an early-stage renal cell neoplasm and warrants further investigation.

Perinephric myxoid pseudotumor of fat: a multimodality imaging case series.

Perinephric myxoid pseudotumor of fat (PMPF) is an unusual clinical entity with few prior imaging case reports. We report a multimodality imaging case series of PMPF, consisting of four cases seen in our department with both imaging studies and histopathologic confirmation. Three of the four patients had a history of advanced non-neoplastic renal disease. The perirenal masses in these cases varied in size and appearance. Some lesions resembled cysts or contained macroscopic fat. Enhancement was equivocal on CT, but prominent in one case on MRI and in another on contrast-enhanced ultrasound. Although not known to be malignant, PMPF may be confused for a cyst, liposarcoma, or hypovascular solid neoplasm on imaging. The dominant mass was resected in two cases because of concern for malignancy, while percutaneous CT-guided biopsy was performed in the other two. Mouse double minute 2 (MDM2) gene amplification by fluorescence in situ hybridization (FISH) was negative in all four cases, excluding well-differentiated liposarcoma. Radiologists should be familiar with PMPF to provide appropriate guidance on clinical management.

Basic nephropathology for pathologists-part1 : Kidney biopsy-inflammation and immune complexes

The assessment of kidney biopsies is mainly confined to specialized centres. However, sometimes akidney biopsy is submitted to ageneral pathologist, and in addition peritumorous renal parenchyma in tumour nephrectomies can have concomitant non-neoplastic renal disease. Here we present asurvey of inflammatory and immunologic changes in all renal compartments, which may in part indicate the need of prompt therapeutic intervention such as in vasculitis, glomerulonephritis and interstitial nephritis. It is important to take into account that renal involvement of vasculitis is mainly centred in glomeruli and only to amuch lesser extent in arteries, and that the frequently observed interstitial inflammation very often is an epiphenomenon of another primary kidney disease and not an independent disease process. Typical renal patterns of injury are emphasised.

Histomorphological assessment of non-neoplastic renal diseases at autopsy: an institutional experience in Southwestern Nigeria.

Autopsy remains an invaluable resource for medical education and establishing diagnosis of diseases that were missed prior to death. Many patients on admission in hospitals suffer kidney diseases that may contribute to their morbidity and/or mortality. The kidneys from autopsies provide opportunity to diagnose and understand some of these non-neoplastic renal lesions. This study aimed to present the frequency of non-neoplastic renal diseases at autopsy. We conducted a five-year retrospective review of post-mortem records of deceased who had autopsy. Data such as age, sex, cause of death, and kidney lesions were extracted from the post-mortem records and clinical details were gotten from the clinical summaries in the autopsy reports. The kidneys were examined for pathological findings that were then classified into glomerular, tubulointerstitial (tubulointerstitial nephritis and other tubular lesions such as tubular necrosis, casts and fibrosis) and vascular lesions. A total of seventy (70) cases met the inclusion criteria with 91.4% having significant non-neoplastic renal lesions. The mean age of the deceased was 57.7years (18years - 91years). Males accounted for 65.7% of the cases. Glomerular lesions were seen in 84.3% of the cases, tubulointerstitial nephritis in 41.6% of cases, vascular lesions were seen in 30% of the cases and other tubular lesions (such as stones, casts and tubular necrosis) were seen in 52.9% of the cases. Cardiovascular diseases and infections were the major causes of death in these patients, accounting for 40% and 27% respectively. Renal diseases were attributed to immediate cause of death in 10% of the cases. The kidney at autopsy provides a valuable renal pathology educational tool, as a wide range of medical renal lesions can be seen from kidneys examined at post mortem.

Study of paediatric renal biopsies with clinicopathologic correlation and comparison with literature on adult renal biopsies

Introduction: Renal biopsy is frequently used in complete work-up for renal diseases. The kidney reacts in a limited number of patterns to various injuries and the clinical manifestations corresponding to these reactions are also limited. Aim of the study: To study the non-neoplastic renal diseases in paediatric population 0-15 year age, to study the differences in the disease prevalence between paediatric and adult population, and to document the geographic variation in renal diseases. Materials and Methods: The renal biopsies from 0-15 year age group of both genders were studied for light microscopy and immunofluorescence studies. The clinical presentation of the patients such as nephrotic or nephritic or both or as acute renal failure was noted for clinic pathologic correlation. The paediatric renal diseases were compared with adult renal diseases based on literature search. Also the geographic variations were studied and compared based on published data from different countries. Results: Nephrotic syndrome was the most common clinical presentation for paediatric renal diseases .Minimal change disease (37.8 %) and FSGS (22.4 %) cases commonly presented as nephrotic syndrome. PIGN (37.6 % cases) presented frequently as nephritic syndrome in the paediatric age group. Conclusion: Nephrotic syndrome is the most common indication for renal biopsy and minimal change disease is the commonest cause of nephrotic syndrome in children. Incidence of membranous nephropathy and IgA nephropathy is relatively less in India. PIGN is the most common cause of acute renal failure in the paediatric age group. In systemic lupus erythematosus, most common presentation is nephrotic syndrome with class IV lupus nephritis being more frequent. Keywords: Acute renal failure, IgA nephropathy, Nephrotic syndrome, Nephritic syndrome, Paediatric age group, Renal biopsy.

Analysis of nonneoplastic medical renal diseases in tumor nephrectomy specimens predicting future renal function

Introduction: Nephrectomy for renal tumor leads to decline in global renal function. The pattern of pathological changes in uninvolved renal parenchyma of nephrectomy specimen is useful to predict the future renal function. Aim: The aim of the present study is to analyze the spectrum of medical renal diseases in nonneoplastic renal parenchyma of tumors nephrectomies and preexisting comorbidities to predict future renal function. Materials and Methods: A prospective study was conducted on 100 nephrectomy patients during the period from November 2015 to February 2019. Nonneoplastic renal parenchyma of nephrectomy specimens was analyzed for the presence of any pathological changes. Serum creatinine levels at preoperative and 6 months after nephrectomy were recorded. Results: Medical renal disease in uninvolved renal parenchyma detected in 52% of cases and arterionephrosclerosis (28%) followed by diabetic nephropathy (10%) was most frequently seen. Diabetes mellitus (DM) and/or hypertension (HTN) were significantly associated with increase in arteriolar hyalinosis, glomerulosclerosis, and interstitial fibrosis/tubular atrophy (P

SAT-336 Non-Neoplastic Renal Diseases Are Common and Underdiagnosed in Nephroureterectomy Specimens

The relationship between chronic kidney disease and renal malignancies is increasingly being recognized. Non-neoplastic kidney diseases can be diagnosed in up to 15% of tumor nephrectomy specimens from kidney cancer patients. We conducted this study to evaluate the non-neoplastic renal parenchyma of nephroureterectomy specimens of urothelial neoplasia of the renal pelvis.

Perinephric myxoid pseudotumor of fat: a distinctive pseudoneoplasm most often associated with non-neoplastic renal disease

In 2009, Tanas et al reported unusual changes in the perinephric fat, mimicking well-differentiated liposarcoma. We report 11 perinephric masses showing similar changes but chiefly arising in patients with non-neoplastic renal disease. Tissue from 11 perinephric masses was retrieved, and immunohistochemistry for IgG/IgG4 and fluorescence in situ hybridization (FISH) for MDM2 amplification was performed. Clinical information was obtained. Cases occurred in 10 males and 1 female (43-84 years of age; median, 63.5 years). Ten patients presented with perinephric masses (size range, 2-28 cm), and one was an incidental finding. Four patients had bilateral or multiple masses. Underlying renal disease included diabetes mellitus (n = 3), end-stage kidney (n = 2), diabetes and end-stage kidney disease (n = 1), chronic pyelonephritis (n = 1), and non-invasive high-grade papillary urothelial carcinoma of the renal pelvis (n = 1). Three patients were not known to have renal disease. Most tumors were submitted as "well-differentiated liposarcoma." The masses consisted of mature fat, myxoid stroma, moderately variable spindled to stellate cells and a mixed inflammatory cell infiltrate. Enlarged, hyperchromatic stromal cells were absent. IgG4-positive plasma cells and MDM2 amplification were absent in all tested cases. Clinical follow-up (11 patients; range, 1-120 months; median, 24 months) showed absent or stable disease in 9 patients; 2 died of unrelated causes. This distinctive pseudoneoplasm usually occurs in association with non-neoplastic renal disease, although similar changes may be identified in the perinephric fat of patients with renal carcinoma. Morphologic evaluation and FISH for MDM2 amplification should allow its distinction from liposarcoma and other mimics.

Diagnosis of non-neoplastic renal diseases in renal mass biopsies

Purpose: As up to 25% of renal neoplasms may be benign, renal function preservation is often a priority in the management of small renal masses. Studies have demonstrated the occurrence of non-neoplastic renal diseases in nephrectomy specimens, but this has not been studied in the setting of renal mass biopsy. Therefore, we conducted this study to determine the feasibility of evaluating the non-neoplastic renal parenchyma in such a limited tissue sample. Methods: We identified 117 needle biopsies for renal lesions in adults from the Department of Pathology archives (2007–2017). Additional stains for periodic acid–Schiff or Jones methenamine silver were obtained as needed. Results: Of 117 cases, non-neoplastic renal parenchyma was absent in 91 cases (78%) and present in 26 cases (22%). Review of the hematoxylin and eosin slides identified 6 cases (5%) with significant diffuse and/or nodular mesangial sclerosis. Additional review of the periodic acid–Schiff and Jones’ stains demonstrated two cases that showed diffuse and focally nodular mesangial sclerosis that was consistent with diabetic nephropathy. Conclusions: The needle biopsy is increasingly useful in guiding the management of patients with small renal masses. Although less than 25% of renal mass biopsies had sufficient non-neoplastic renal parenchyma for pathologic evaluation, medical renal diseases, such as diabetic nephropathy, could be diagnosed. On the contrary, the biopsy specimens for urothelial lesions rarely yield sufficient adjacent non-neoplastic renal parenchyma for pathologic evaluation.

Pattern of glomerulonephritis in the Kashmir valley.

Glomerulonephritis (GN) is a common cause of end-stage kidney disease (ESKD) that can affect patients at any age. With respect to ESKD, there are significant global variations in the percentage of the incident and prevalent patients secondary to GN. The present study was therefore conducted to know the pattern of GN in the Kashmir valley. Retrospective study was conducted in the tertiary center Sher-I-Kashmir Institute of Medical Sciences of Kashmir valley which included cases of different types of GN diagnosed on histopathology over a period of three years. Basic demographic profile including age, sex, clinical presentation, relevant investigations, and the histopathological type of GN was noted for each patient. Histopathological examination due to various nonneoplastic renal diseases was done in 336 cases and out of these, glomerular diseases were diagnosed in 298 cases. Proteinuria and edema was the most common presentation. Primary GN was observed in 81% of cases and secondary GN in 16% of cases. IgA nephropathy was the most common primary GN 42% and nephropathy due to lupus was the most common secondary GN. The study concluded that primary GN is the most common primary renal disease with IgA as the most common primary GN and most presented as renal failure, highest until date recorded in India and lupus nephritis as the most common secondary GN which is similar to other studies from India and other regions of the world. This study may be useful to pathologists, nephrologists, and health care providers to formulate a basic platform for effective diagnostic, therapeutic, and research base for glomerular diseases so as to prevent its complications.

An analysis of adult non-neoplastic nephrectomies at a tertiary care centre in Mumbai

Introduction: Nephrectomies are an integral part of urological practice and a wide range of renal diseases are seen on histopathological examination of non-neoplastic nephrectomy specimens. Objective: The objective of this study was to assess the incidence, clinical presentation and the histological spectrum of various non-neoplastic renal diseases detected in nephrectomy specimens at our institute and to compare our observations with the conventional patterns seen. Material and Methods: This is a retrospective 6 year study of adult non-neoplastic nephrectomies (ANNN) conducted in a tertiary care centre in Mumbai and includes 359 cases from January 2009 to December 2015. The paraffin blocks and slides were retrieved from our archives and analysed along with clinical features, radiological findings. Results: 359 ANNN specimens received over a 6 year period were studied. Most of the patients were in the sixth decade with a slight female preponderance. Flank pain was the commonest presenting symptom seen in 79.94% of cases. The most frequent surgical indication for ANNN was obstructive uropathy (47.08%) which includes calculus disease and PUJ obstruction followed by non-functioning kidney (42.06%). On histopathological examination, the most common gross pathology was acalculus hydronephrosis (40.67%) and the most frequent histopathological diagnosis was chronic pyelonephritis seen in 79.38% cases. Calculus obstructive uropathy amounted to 39.27% cases and acalculus obstructive uropathy amounted to 25.07% cases of chronic pyelonephritis. Conclusion: The most frequent surgical indication was obstructive uropathy and the most common histopathological diagnosis was chronic pyelonephritis. Calculus and acalculus obstructive uropathy amounted to almost 65% of the cases of chronic pyelonephritis.

Renal histologic parameters influencing postoperative renal function in renal cell carcinoma patients.

BackgroundPre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma.MethodsOne paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated.ResultsAmong the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered.ConclusionsIn conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.

Role of Electron Microscopy in the Diagnosis of Nonneoplastic Renal Disease in Children

To assess the role of electron microscopy in the evaluation of pediatric renal biopsies, all native kidney biopsies performed in children for nonneoplastic renal disease over a 2-year period were reviewed. Of 80 biopsies, the role of electron microscopy was classified as “essential” in 50 (63%), “supportive or confirmatory” in 18 (23%), and “noncontributory” in 9 (11%), with no glomeruli available for study in 3 (4%). The role of electron microscopy with respect to indication for biopsy and final diagnosis is discussed. This study confirms the continued importance of electron microscopy in the evaluation of pediatric renal biopsies.

Non-neoplastic Renal Diseases are Often Unrecognized in Adult Tumor Nephrectomy Specimens

The pathologic evaluation of tumor nephrectomy specimens focuses on the diagnosis, grading, and staging of the neoplasm. The presence of coincidental non-neoplastic diseases in these specimens may have significant implications for patient outcomes. The purpose of this study is to determine the spectrum of non-neoplastic disease processes that may be overlooked in tumor nephrectomies, and to ascertain the extent to which surgical pathologists are trained to recognize these lesions. We reviewed the hematoxylin and eosin-stained slides of 246 adult tumor nephrectomy specimens with an emphasis on the non-neoplastic renal parenchyma. Further analysis of cases with pathologic alterations included special stains and direct immunofluorescence microscopy. The surgical pathology reports were reviewed to determine whether the non-neoplastic lesions were originally identified. We also surveyed United States pathology residency programs to determine how many require training in medical renal pathology. Forty-one cases (16.7%) had alterations, such as diffuse and/or nodular mesangial sclerosis, mesangial hypercellularity, or glomerular basement membrane thickening that warranted further study. After further work-up and clinical correlation, the pathologic changes in 24 cases were categorized as follows: diabetic nephropathy (19 cases) of which one demonstrated atheroembolic disease, thrombotic microangiopathy (3 cases), sickle cell nephropathy (1 case), and focal segmental glomerulosclerosis (1 case). Twenty-one (88%) of these diagnoses were not identified at initial pathologic evaluation. Only 35 of 98 pathology residency programs that responded to our survey require any formal training in medical renal pathology. Although accurate pathologic evaluation of renal neoplasms remains essential, surgical pathologists should be aware that coincidental non-neoplastic renal diseases are common, often not recognized, and may have important implications for patient care. Further consideration should be given to the training requirements of pathology residents and the guidelines for evaluation of nephrectomy specimens to avoid missing non-neoplastic renal lesions.

Occupational factors and renal disease.

The male-to-female ratio of patients requiring dialysis treatment commonly approaches 2:1. It is proposed that environmental factors, particularly occupational exposure to hydrocarbons, may account for the excess number of male patients. The term "hydrocarbon" refers to the aliphatic, alicyclic, aromatic, and halogenated hydrocarbons (carbon tetrachloride, chloroform); glycols (ethylene glycol, diethylene glycol, dioxane, glycerol); and organic solvents. Hydrocarbons commonly find use as solvents in industrial manufacturing practices because of their lipid solubility. Hydrocarbons have long been known to be neurotoxicants, affecting both peripheral and central nervous systems. Although benzene and its derivative have a known association with uroepithelial tumors, there is now a considerable body of evidence suggesting a possible role for hydrocarbon exposure in the development of non-neoplastic renal diseases. This article presents an epidemiological case for such an association and critically reviews the literature.

Renal impairment with chronic hydrocarbon exposure

Occupational hydrocarbon exposure is believed by some investigators to play an important role in the development of several non-neoplastic renal diseases. In view of the continuing debate in this area of nephrology we adopted a cross-sectional approach by investigating the prevalence of clinical or sub-clinical renal dysfunction in subjects chronically exposed to hydrocarbons at their work site. Three groups of healthy men working in different and separate areas of a major car manufacturing plant in the North-west of England participated in the study. Group 1 comprised 112 paint sprayers with exposure to paint-based hydrocarbons, group 2 comprised 101 volunteers working in the transmission area of the plant with exposure to petroleum-based mineral oils, and group 3 comprised 92 automated press operators with minimal background exposure to lubricants who acted as internal controls. Early markers of renal dysfunction such as serum creatinine, urinary total protein, albumin, transferrin, retinol binding protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion were measured. Upper reference values of the parameters measured were derived from 105 comparable laboratory based controls with no occupational exposure to hydrocarbons or heavy metals. Group 1 had a significantly higher prevalence of elevated serum creatinine than the other groups and a higher prevalence of abnormal urinary total protein, N-acetyl-glucosaminidase, gamma-glutamyl transferase, and leucine-amino-peptidase excretion than groups 2 and 3. Group 2 had normal serum creatinine but a significantly higher prevalence of abnormal urinary total protein, transferrin, retinol binding protein, N-acetyl-glucosaminidase, and leucine-amino-peptidase excretion than group 3. Serum albumin was similar in all groups. There was some clustering of abnormal findings but the markers of renal dysfunction used in the study identified 37 individuals in group 1 and 31 subjects in group 2 with at least one abnormal parameter, compared to only five individuals in internal controls. This difference between the two target groups and group 3 was highly significant (p < 0.001). Subjects with chronic paint exposure had renal impairment and tubular dysfunction. Tubular dysfunction was also prominent with petroleum oil exposure. We therefore conclude that chronic hydrocarbon exposure may be associated with clinical and sub-clinical renal dysfunction. We advocate careful monitoring of workers exposure to hydrocarbons and for more effective preventive measures.

Strain differences of I-compounds in relation to organ sites of spontaneous tumorigenesis and non-neoplasticrenal disease in mice

Possible associations between the patterns and levels of I-compounds (putative endogenous, age-dependent, adduct-like DNA derivatives) and the incidence of spontaneous tumors and renal diseases in mice were investigated by 32P-postlabeling assay. Liver, lung and kidney DNAs of 8-10 month old inbred male mice of strains C57BL, C3H, CBA, A and RFM were examined. It was found that liver DNA of the C3H mouse, known to develop a high incidence of spontaneous hepatomas, and lung DNA of the A mouse, known to have a high incidence of spontaneous lung tumors, contained smaller numbers and significantly lower total levels of I-compounds as compared with the resistant C57BL mouse. Kidney DNA of C57BL, C3H and A mice presented significantly higher levels of I-compounds compared with those of CBA and RFM mice, both of which are known for exceptionally high incidences of spontaneous renal diseases. Total kidney I-compound levels in CBA and RFM mice were only 30-40% of those found in C3H, A and C57BL. Reduced I-compound levels observed in the three organs thus tended to be associated with spontaneous tumorigenesis and degenerative disease in susceptible strains, suggesting that I-compounds may be important for normal gene transcription and DNA replication. On the other hand, some of these DNA derivatives may, as adduct-like premutagenic lesions, contribute to spontaneous tumorigenesis. This was suggested by the finding that CBA mice which exhibit moderate spontaneous hepatoma incidence, had higher levels of certain I-compounds in their liver DNA although the total levels were not significantly different compared with those in C57BL mice. The observations of the present study suggest that (i) the patterns and levels of I-compounds are genetically determined and (ii) lack or excess of these DNA modifications may result in adverse health effects; however, this may not always be the case, for example, if modulating factors exist which compensate for I-compound deficiency.

Hydronephrosis and polycythemia: A case of erythrocytosis relieved by decompression of unilateral hydronephrosis and cured by nephrectomy

A case of erythrocytosis relieved by decompression and drainage of unilateral hydronephrosis and cured by nephrectomy is reported. The remission, which was complete within the twenty-five days comprising the drainage and postnephrectomy periods, was chiefly due to depression of erythropoiesis. The characteristics and rate of remission of erythrocytosis during drainage and postnephrectomy periods were similar, suggesting that both caused withdrawal of an excessive stimulus to erythropoiesis. Since erythropoietin or its precursor may originate in the kidney, the compression of renal parenchyma by hydronephrosis and decompression by drainage could have influenced the production of erythropoietin by the affected kidney. The high incidence of congenital anomalies of the urinary tract in cases of non-neoplastic renal disease associated with erythrocytosis suggests that both a congenital anomaly and an intrarenal space-occupying lesion may be necessary for renal erythrocytosis to develop.