Tubular and interstitial disease

2021 ◽  
pp. 140-184
Keyword(s):  
Tubulointerstitial Nephritis ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Disease Process ◽  
Analgesic Nephropathy ◽  
Tubular Epithelium ◽  
Tubular Atrophy ◽  
Important Group ◽  
The World ◽  
Interstitial Disease

Tubulointerstitial diseases refer to a group of disorders in which inflammatory cell infiltrates within the kidney interstitium and/or tubular epithelium are seen on kidney biopsy. These disorders constitute an important group of kidney diseases with varying prevalences and presentations due to a number of causes. It is difficult to estimate the worldwide incidence of tubular and interstitial disease as it is a histological diagnosis and biopsy rates vary substantially around the world. Increasing incidence of tubulointerstitial nephritis has been related to polypharmacy, particularly in the older population. Tubulointerstitial nephritis may present acutely as an immunologically mediated hypersensitivity reaction to an inciting agent—typically a drug or infection—or chronically as a part of a disease process leading to chronic interstitial fibrosis and tubular atrophy. Allergic interstitial nephritis, analgesic nephropathy, nephrotoxic metals, hyperuricemia, Balkan nephropathy, Mesoamerican nephropathy, aristolochic acid nephropathy, and other rare causes of tubulointerstitial nephritis are covered in this section. Isolated defects of tubular function, tubular disorder-related nephropathies, and electrolyte derangements also constitute important aspects of tubulointerstitial diseases.

Interstitial renal disease

2018 ◽  
Author(s):  
William G. Herrington ◽  
Aron Chakera ◽  
Christopher A. O’Callaghan
Keyword(s):  
Renal Disease ◽  
Interstitial Nephritis ◽  
Tubulointerstitial Nephritis ◽  
Interstitial Fibrosis ◽  
Acute Interstitial Nephritis ◽  
Renal Diseases ◽  
Interstitial Tissue ◽  
Renal Tubules ◽  
Early Disease ◽  
Tubular Atrophy

Tubulointerstitial renal diseases affect the renal tubules and/or the supporting interstitial tissue around them. The glomeruli are typically spared in early disease. Acute interstitial nephritis is characterized by an inflammatory infiltrate (often containing eosinophils). Chronic tubulointerstitial nephritis (TIN) is characterized by extensive tubular atrophy and interstitial fibrosis. The processes are clinically distinct but a prolonged acute interstitial nephritis will develop into chronic disease. This chapter looks at the etiology of interstitial renal disease, as well as its symptoms and clinical features, demographics, complications, diagnosis, and treatment.

Drug-induced chronic tubulointerstitial nephritis

2015 ◽  
Author(s):  
Hassan Izzedine ◽  
Victor Gueutin
Keyword(s):  
Renal Disease ◽  
Drug Exposure ◽  
Tubulointerstitial Nephritis ◽  
Chemotherapeutic Agents ◽  
Analgesic Nephropathy ◽  
Small Subset ◽  
Low Grade ◽  
Tubular Dysfunction ◽  
Drug Induced ◽  
Tubular Atrophy

The chronic form of drug-induced tubulointerstitial nephritis (CTIN) is an insidious disease and most probably represents the common final response pattern of the kidney to a variety of agents (including analgesics, lithium, antineoplastic chemotherapeutic agents, like cisplatin and nitrosoureas, and immunosuppressive drugs, such as ciclosporin and tacrolimus). Drug-induced CTIN is usually asymptomatic, presenting with slowly progressive renal impairment. Because of its insidious nature, CTIN is often diagnosed incidentally on routine laboratory screening or evaluation of CKD. The diagnosis of drug-induced CTIN largely depends on the history of exposure to a nephrotoxic drug. Clinical investigations may show modest elevation in serum creatinine, evidence of tubular dysfunction (e.g. renal tubular acidosis), or Fanconi syndrome (i.e. aminoaciduria, glycosuria, hypophosphataemia, and hypouricaemia). Urinalysis may be normal or show low-grade proteinuria (< 1.5 g/day) and/or pyuria. Diagnosis depends on renal biopsy, which reveals variable cellular infiltration of the interstitium, tubular atrophy, and fibrosis. Analgesic nephropathy is possibly still the most common category of CTIN worldwide. The amount of phenacetin-acetaminophen combination required to cause CTIN has been estimated to be at least 2–3 kg over many years. Lithium-induced CTIN occurs in a small subset of patients receiving long-term lithium therapy, who have had repeated episodes of lithium toxicity, with high serum drug levels. CTIN induced by ciclosporin or tacrolimus is common among patients receiving kidney, heart, liver, and pancreas transplants. The mechanism appears to be dependent largely on the potent vasoconstrictive effects of these drugs. The recognition of a potential association between a patient’s renal disease and exposure to a drug is crucial, because, unlike many other forms of renal disease, drug-induced CTIN can be prevented and even reversed, by avoiding additional drug exposure.

scholarly journals Proteomic Study of Low-Birth-Weight Nephropathy in Rats

2021 ◽  
Vol 22 (19) ◽  
pp. 10294
Author(s):  
Toshiyuki Imasawa ◽  
Stéphane Claverol ◽  
Didier Lacombe ◽  
Nivea Dias Amoedo ◽  
Rodrigue Rossignol
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Respiratory Chain ◽  
Interstitial Fibrosis ◽  
Early Stage ◽  
Disease Process ◽  
Mitochondrial Respiratory Chain ◽  
Kidney Cortex ◽  
Tubular Atrophy ◽  
Mitochondrial Respiratory

The hyperfiltration theory has been used to explain the mechanism of low birth weight (LBW)-related nephropathy. However, the molecular changes in the kidney proteome have not been defined in this disease, and early biomarkers are lacking. We investigated the molecular pathogenesis of LBW rats obtained by intraperitoneal injection of dexamethasone into pregnant animals. Normal-birth-weight (NBW) rats were used as controls. When the rats were four weeks old, the left kidneys were removed and used for comprehensive label-free proteomic studies. Following uninephrectomy, all rats were fed a high-salt diet until 9 weeks of age. Differences in the molecular composition of the kidney cortex were observed at the early step of LBW nephropathy pathogenesis. Untargeted quantitative proteomics showed that proteins involved in energy metabolism, such as oxidative phosphorylation (OXPHOS), the TCA cycle, and glycolysis, were specifically downregulated in the kidneys of LBW rats at four weeks. No pathological changes were detected at this early stage. Pathway analysis identified NEFL2 (NRF2) and RICTOR as potential upstream regulators. The search for biomarkers identified components of the mitochondrial respiratory chain, namely, ubiquinol-cytochrome c reductase complex subunits (UQCR7/11) and ATP5I/L, two components of mitochondrial F1FO-ATP synthase. These findings were further validated by immunohistology. At later stages of the disease process, the right kidneys revealed an increased frequency of focal segmental glomerulosclerosis lesions, interstitial fibrosis and tubular atrophy. Our findings revealed proteome changes in LBW rat kidneys and revealed a strong downregulation of specific mitochondrial respiratory chain proteins, such as UQCR7.

scholarly journals Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease: Results from the Boston Kidney Biopsy Cohort

2021 ◽  
Author(s):  
Insa M. Schmidt ◽  
Suraj Sarvode Mothi ◽  
Parker C. Wilson ◽  
Ragnar Palsson ◽  
Anand Srivastava ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Disease Progression ◽  
Multiple Testing ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Future Research ◽  
Tubular Atrophy ◽  
Kidney Disease Progression ◽  
Kidney Injury Molecule 1

AbstractBackgroundBiomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease.MethodsUsing a proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semi-quantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or ESKD) and death.ResultsAfter multivariable adjustment and correction for multiple testing, 46 proteins associated with different histopathologic lesions. The top performing markers positively associated with acute tubular injury and interstitial fibrosis and tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and immunoglobulin domain-containing protein 2 (VSIG2). 30 proteins were significantly associated with kidney disease progression and 35 with death. The top performing markers for kidney disease progression were placental growth factor (PGF; HR 5.4, 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (BAMBI; HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (TRAIL-R2; HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (CDCP1; HR 2.4, 95% CI 1.8, 3.3).ConclusionWe identified several biomarkers associated with kidney disease histopathology and prognosis – many of which have not been reported previously and may represent important avenues for future research.

scholarly journals The Oxford Classification of IgA nephropathy: A review of literature

2018 ◽  
Vol 8 (1) ◽  
pp. 1308-1312
Author(s):  
Anil Dev Pant
Keyword(s):  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Asian Population ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Mesangial Proliferation ◽  
Primary Glomerulonephritis ◽  
The World ◽  
The Oxford Classification

IgA nephropathy is one of the commonest forms of primary glomerulonephritis in the world, most commonly among Asian population.  Though usually slowly progressive, it is one of the important causes of chronic renal failure. Abnormal IgA1 are formed which leads to formation of IgG antibodies which deposit in the mesangium.  It presents with synpharyngitic hematuria and can have variable histopathological patterns.  The Oxford classification was devised in order to categorize the histopathological patterns, correlate with clinical course and modify treatment accordingly.  Different histopathological criteria are assessed in the classification, which include mesangial proliferation (M), endocapilary proliferation (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T).The classification has become widely accepted around the world but still needs further validation studies and incorporation of newer parameters. 

Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease

2021 ◽  
pp. CJN.09380721
Author(s):  
Insa Schmidt ◽  
Suraj Sarvode Mothi ◽  
Parker Wilson ◽  
Ragnar Palsson ◽  
Anand Srivastava ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Disease Progression ◽  
Multiple Testing ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Protein Biomarkers ◽  
Tubular Atrophy ◽  
Kidney Disease Progression ◽  
Kidney Injury Molecule 1

Background: Biomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease. Methods: Using a proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semi-quantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of kidney replacement therapy) and death. Results: After multivariable adjustment and correction for multiple testing, 57 proteins were associated with different histopathologic lesions. The top performing markers positively associated with acute tubular injury and interstitial fibrosis and tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and immunoglobulin domain-containing protein 2 (VSIG2), respectively. 30 proteins were significantly associated with kidney disease progression and 35 with death. The top performing markers for kidney disease progression were placental growth factor (HR per doubling 5.4, 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (HR 2.4, 95% CI 1.8 to 3.3). Conclusion: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases.

scholarly journals Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Xiao ◽  
Ajay K. Medipally ◽  
Laura Biederman ◽  
Anjali A. Satoskar ◽  
Iouri Ivanov ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Smooth Muscle Actin ◽  
Heme Oxygenase 1 ◽  
Common Symptom ◽  
Tubular Epithelial Cells ◽  
Tubular Atrophy ◽  
Mesenchymal Transition

Chronic kidney disease (CKD) is a common outcome of many kidney diseases. Interstitial fibrosis and tubular atrophy (IFTA) is a histologic hallmark of CKD. Hematuria is a common symptom in many human kidney diseases. Free hemoglobin may affect tubular epithelial cells by generating reactive oxygen species (ROS). Epithelial–mesenchymal transition (EMT) of the tubular epithelial cells has been shown to play an important role in the IFTA development. The aim of this study was to determine the effects of chronic hematuria on the CKD progression in 5/6 nephrectomy (5/6NE) rat model of CKD. 5/6 NE rats were treated with oral warfarin (0.5 mg/kg/day) or vehicle (control). The animals were monitored for 26 weeks, while prothrombin time (PT), serum creatinine (SCr), and hematuria were measured weekly. Staining for iron, trichrome, and EMT (vimentin, E-cadherin, smooth muscle actin) markers was performed on the remnant kidneys. ROS were detected in the kidneys by protein carbonyl assay and immunohistochemistry for heme oxygenase 1 (HMOX1), at the end of the study. Apoptosis was detected by TUNEL assay. Warfarin treatment resulted in a PT increase 1.5–2.5 times from control and an increase in hematuria and SCr. Histologically, warfarin-treated animals had more iron-positive tubular epithelial cells and increased IFTA as compared to control (42.9 ± 17% vs. 18.3 ± 2.6%). ROS were increased in the kidney in warfarin-treated rats. The number of tubules that show evidence of EMT was significantly higher in warfarin-treated 5/6NE as compared to control 5/6NE rats. The number of apoptotic tubular epithelial cells was higher in warfarin-treated 5/6 NE rats. Chronic hematuria results in increased iron-positive tubular epithelial cells, EMT, apoptosis, and more prominent IFTA in CKD rats. Our data suggest an important role of chronic hematuria in the progression of CKD.

Healthcare apps on smartphones available in Brazil: a preliminary classification (Preprint)

2020 ◽  
Author(s):  
André De Faria Pereira Neto ◽  
Leticia Barbosa ◽  
Rodolfo Paolucci
Keyword(s):  
Health Promotion ◽  
Disease Prevention ◽  
Digital Health ◽  
Disease Process ◽  
World Health ◽  
Computing Device ◽  
Care Treatment ◽  
Wide Range ◽  
The World ◽  
Health Applications

UNSTRUCTURED Billions of people in the world own a smartphone. It is a low-cost, portable computing device with countless features, among which applications stand out, which are programs or software developed to meet a specific goal. A wide range of applications available ranging from entertainment and personal organization to work and education is available currently. It is a vast and profitable market. Health applications have been a means of intervention for different areas, including chronic diseases, epidemics, and health emergencies. A recently published paper in the journal with the highest impact factor in Digital Health (“Journal of Medical Internet Research”) proposes a classification of health applications. This study performs a critical analysis of this organization and presents other sort criteria. This paper also presents and analyzes the “Meu Info Saúde” (“My Health Info”) app – a pioneering government initiative focused on primary care launched by the Oswaldo Cruz Foundation. The application classification proposal that will be presented builds on the intervention strategies in the health-disease process, namely: “Health Promotion”, “Disease Prevention” and “Care, Treatment and Rehabilitation”, as defined by official documents such as the World Health Organization and the Centers for Disease Control and Prevention. Most applications present in the sample are of private and foreign origin, free to download, but with a display of ads or the sale of products and services. The sampled applications were classified as “Health Promotion”, and some applications have also been categorized as “Disease Prevention” or “Care, Treatment or Rehabilitation” because they have multiple functionalities. The applications identified as “Health Promotion” focused only on individuals’ lifestyle and their increased autonomy and self-care management capacity. From this perspective, the apps analyzed in this paper differ from the “Meu Info-Saúde” application developed at Fiocruz.

Identifying patients with CKD risk at the time of nephrectomy: When to initiate nephrology consult

2021 ◽  
pp. 239936932110319
Author(s):  
Yihe Yang ◽  
Zachary Kozel ◽  
Purva Sharma ◽  
Oksana Yaskiv ◽  
Jose Torres ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Radical Nephrectomy ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Interstitial Fibrosis ◽  
Kidney Neoplasm ◽  
Tubular Atrophy ◽  
Independent Risk Factors

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.

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