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Tubulointerstitial Nephritis

Tubulointerstitial Nephritis

Article Author:
Jenish Bhandari
Article Author:
Pawan Thada
Article Editor:
Hasan Arif
11/23/2020 7:02:42 AM
For CME on this topic:
Tubulointerstitial Nephritis CME
PubMed Link:
Tubulointerstitial Nephritis


Tubulointerstitial nephritis (TIN) is a group of immune-mediated inflammatory disease that involves the interstitium and tubules. Inflammation of the kidney consists of the collection of inflammatory cells, fluid, and extracellular matrix surrounding the interstitium along with the infiltration of tubular cells by inflammatory cells that define both tubules and interstitium pathology. It is one of the most important and major causes of acute kidney injury that subsequently drives to renal failure. TIN can be classified into acute and chronic on the basis of underlying etiology, duration, or histology.[1] Renal impairment with acute TIN is reversible provided that early and appropriate interventions are made but, chronic TIN may be irreversible in severe cases. Drug-induced nephritis is widely described and is the leading cause of TIN. Delay in diagnosis due to nonspecific signs and symptoms is frequently seen; thus, many attempts have been made for effective diagnosis and exclude the other differentials carefully through efficient clinical experts' opinions and assessment and diagnostic tests.


There are multiple causative factors of tubulointerstitial nephritis like drug-induced, idiopathic, genetic, immune-mediated, infectious (viral, bacterial, parasitic or fungal), associated systemic inflammatory condition such as inflammatory bowel disease, sarcoidosis, systemic lupus erythematosus (SLE), Sjögren disease, immunoglobulin G4 associated autoimmune disease (interstitial infiltration of IG4 positive plasma cell and C3 deposition), tubulointerstitial nephritis and uveitis syndrome.[2] The most important etiology is medication (beta-lactam antibiotics, sulphonamides, proton pump inhibitors, 5-aminosalicylates, rifampicin, and NSAIDs) which consists of 50% to 80% sometimes up to 92% of the total cases, idiopathic 8%, and other 15%.[3][4][3] The most common etiology among medications is NSAIDs (44%), followed by antibiotics (33%), proton pump inhibitors (7%).[5] TIN is the third leading cause of renal transplant dysfunction, whereas transplant rejection in already immunocompromised patients is mainly due to infections, including polyomavirus or cytomegalovirus. Bone marrow transplant recipients are mainly associated with necrotizing TIN due to adenovirus. TIN and uveitis syndrome is associated with Epstein-Barr virus and bacteria like leptospira, mycoplasma, and yersinia.[6][7] Anti tubular basement membrane antibodies also involved in TIN. In most cases of TIN by a bacteria, renal pelvis is prominently involved; hence the definitive term pyelonephritis is used. Term interstitial nephritis generally is reserved for cases of TIN that are nonbacterial in origin, i.e., tubular injury by drugs, hypokalemia, immune reactions (autoimmune), irradiation, viral infections. The TIN antigen is an extracellular basement membrane protein, and the deletion of TIN antigen leads to disruption of the basement membrane structure predisposing to the TIN.[2] 


Acute TIN is the leading cause of acute kidney injury (AKI). The overall global prevalence of acute TIN is 1% to 3%, among all renal biopsies and the overall prevalence of acute TIN increased to 15% to 27%, when the analysis was restricted to only AKI cases.[8][9][10][11][12][9] Analysis of kidney biopsy registries from 120 hospitals in Spain affirmed 2.7% of acute TIN and 17% of which complicated to acute kidney injury. When only AKI patients were analyzed, the prevalence was increased to 13% in Spain, which is similar to elsewhere.[13] In this study, most of the patients accounted for adults and elderly, and only 5% were children, male (53%) compared to females (47%). Data analysis from Czech registries of renal biopsies insisted the rate of TIN was 4%, but when analyzed only among the patients with renal insufficiency, it was around 12%.[14] There is an increase in the incidence of TIN from 3% to up to more than 12% among the older adults, mainly due to the increased use of antibiotics, NSAIDs in that population group.


High metabolic demand and relatively less blood supply make the tubulointerstitium susceptible to injury. Kidney has a higher exposure to drugs and toxins, which increases the chances of renal injury.[15] TIN mainly involves inflammation and edema of the interstitium, which compromises the blood supply further and ultimately causing a decrease in glomerular filtration rate (GFR). The glomerulus is relatively spared and involved only in late and severe stages. Initially, offending agents damage tubular cells and interstitium, causing acute TIN but in long-standing progressive cases sequel to chronic TIN, which is characterized by irreversible deterioration of renal function due to tubular atrophy and fibrosis. Production and activation of cytokines, tissue necrosis factors alpha (TNF-alpha) by inflammatory cells (lymphocytes, macrophages) and renal cells (interstitial fibroblasts, vascular endothelial cells, proximal tubular cells) escalates the inflammatory process. Macrophages are responsible for repair initially but later on contributes to inflammation by producing fibrogenic cytokines, TGF-beta. TGF-beta is responsible for fibrosis in the chronic TIN. Tubular atrophy leads to burnout and the decrease in the number of nephrons, which overwhelm the functioning capacity of remaining nephrons by hyperfiltration leading to CKD. TGF-beta favors the accumulation of collagen in the extracellular matrix and basement membrane and inhibits the collagenase and metalloproteinase enzymes In the setting of tubular necrosis, a complex series of necrosis induced inflammation i.e., neuroinflammation has a role in the pathogenesis of TIN. Injured renal tubular cells losses its polarity, integrity and undergoes apoptosis and necrosis. Necrosed cells express various danger-associated molecular pattern (DAMP) and alarmins, which activates the immune response to induce inflammation. This whole process of intensifying inflammation through necrosed tubular cells is known as necroinflammation.[15][16]

Drug-induced TIN is as a result of allergic reactions and is immune-mediated. Only small proportions of the population taking the same medications have TIN mainly due to variable responses of individuals to the same drug.[17] It is dose-independent and shows systemic manifestations of hypersensitivity.[1] The main pathogenic mechanism of interstitium in the drug-induced TIN is type IV hypersensitive reactions in which T cells (71% CD8+ and CD4+ equally) have central role and monocytes (15%), B cells(7%). Acute tubular injury is due to the direct toxicity of drugs and the progression of inflammatory infiltration of the interstitium.[15] Drugs act as hapten either by mimicking or directly binding to the tubular cells basement membrane that stimulates an immunogenic response in return. Some studies suggest the production of reactive oxygen species (ROS) during oxidative stress induces mitochondrial injury. Damaged mitochondrial membrane integrity releases proapoptotic factors like cytochrome c that induces apoptosis and cell death.[15]

Another mechanism of TIN is due to cell injury and insults by bacterial, viral, fungal infections often associated with preexisting obstruction or reflux. In the absence of obstruction, damage, and loss of functions of tubular cells by bacteria is unlikely as the kidney is resistant to structural damage by a bacterial infection. Pathogenesis of other systemic diseases such as sarcoidosis, inflammatory bowel disease, SLE, granulomatosis with polyangiitis, Sjögren syndrome, etc. is complex, and it is supposed that multiple factors such as susceptibility to autoimmunity, systemic inflammation, genetic predispositions, nutritional insufficiency, predisposed infectious agents are involved.[1]


Interstitial inflammatory cell infiltration and edema are the findings in the histopathologic light microscopy regardless of etiology. Inflammatory cells are most commonly lymphocytes, neutrophils, and plasma cells but, drug-induced TIN associates eosinophils infiltration. Esopisnophil's presence is not absolutely diagnostic of drug indued TIN as NSAIDs don't involve eosinophils due to its anti-inflammatory nature. The presence of dominant neutrophils and plasma cells suggests a bacterial infection.[18][1] Interstitial inflammation is either focal or diffuse. In addition, features of tubulitis, i.e., tubular degenerative changes, irregular luminal contours and ectasia, cytoplasmic simplification, prominent nucleoli, apoptotic figures, and loss of brush border finally tubular atrophy due to tubular infiltration of inflammatory cells.[17][19] Granulomas formation with multinucleated giant cells along with foci of necrosis is rare (0.5%), present in the renal biopsy of tuberculosis, fungal infection, Crohn disease, sarcoidosis, and few drugs. Eventually, this granuloma is replaced by fibrosis.[20]

Immunofluorescence and electron microscopy has fewer features and so not helpful in diagnosis because it is usually negative in patients with drug-induced TIN, and only rarely methicillin induced TIN shows immunoglobulins at the tubular basement membrane. The granular or linear pattern of deposition in immunofluorescence usually indicates autoimmune diseases and minimal change disease treated with NSAIDs.[17] Glomeruli and renal vasculature are usually normal unless in the late disease process, and another superimposed process is also present.

History and Physical

The challenging aspect of TIN is the nonspecific and highly variable clinical presentation that delays the diagnosis and treatment, which eventually worsens the outcome. History of onset and duration, age of the patients, and drug intake is of utmost importance while assessing for TIN. The classical presentation of drug-induced hypersensitivity in a study series showed fever (27%), rash (15%), eosinophilia (23%). The classic triad of fever, rash, and eosinophilia is found to be in only 10% of cases. Even the symptoms may vary in different classes of medications. However, some studies suggest that allergic features dominate the clinical presentations in the drug-induced TIN.[21] In a retrospective study, acute kidney injury due to medications initially presented without oliguria but as the disease worsens and progresses oliguria in 51%, arthralgia in 45%.[5][18] Fever may be absent in drug-induced TIN, including NSAIDs and beta-lactam, but may be present in 50% to 100% cases of methicillin induced TIN. Fever is either low grade or intermittently spiking and usually arise within 2 weeks of medication but present early immediately within hours or days in cases of reinfection.[17] About 75% of beta-lactam users may present with hematuria, leukocyturia, proteinuria. Around two-thirds of patients using rifampicin have associated thrombocytopenia, hepatitis, hemolytic anemia, and proximal tubular cell damage that leads to glycosuria. Common nonspecific symptoms are myalgia, fatigue, weight loss, anorexia, and headache.

On physical examination, skin rashes in the form of morbilliform, maculopapular, erythroderma, and epidermal necrolysis are seen. These rashes are highly variable extrarenal manifestations more common in agents that cause hypersensitive reactions such as penicillins, sulfonamides, phenytoin, allopurinol. The kidney is palpable occasionally in severe cases when markedly enlarged. Flank pain and tenderness due to capsular distension by inflammation and edema are likely in those taking rifampicin.[17] Detectable features of nephrotic syndromes like facial puffiness and pedal edema are sometimes seen too.[20]


Diagnosis may be delayed due to the presence of nonspecific symptoms. It is challenging to differentiate acute and chronic TIN and equally important to separate TIN from other causes of renal disease such as glomerulonephritis and acute tubular necrosis because treatment and prognosis are different. Clinical assessment, laboratory findings, imaging tests are the approaches by clinicians to make the diagnosis.

Renal Biopsy

Histopathological view after the renal biopsy is the only definitive diagnosis and gold standard for TIN, which shows characteristic diffuse or focal inflammatory cells (lymphocytes, plasma cells, neutrophils, eosinophils, histiocytes) infiltration, edema, and fibrosis along with tubulitis. One should always have a high suspicion for TIN in any patient with renal insufficiency. No clinical improvement even after withdrawal of offending agents should be advised for renal biopsy provided that there is no contraindications and patient is agreed.[22] At times, the composition of inflammatory cells may point out the diagnostic etiology such as dominant eosinophils in the drug-induced TIN with few exceptions like NSAIDs where no eosinophils can be seen, and it should be remembered that drug-induced TIN may contain all other types of inflammatory cells. In addition, a histologic manifestation of tubulitis and tubular cell degeneration supports evidence for the diagnosis of TIN.[19]

Imaging Tests

Renal ultrasonography (USG) and CT scans are often used as imaging studies to support the diagnosis of TIN. These tests reveal bilateral normal to the increased size of the kidney and diffusely increased cortical hyperechogenicity.[17] But these ultrasonography findings cannot exclude or confirm the other causes of renal enlargement but helps exclude urinary tract obstruction pinpointing the presence or absence of hydronephrosis.[22] Yet, renal USG and CT scans are helpful in the exhibition of cysts, mass, or stones, so excludes the other causes of acute kidney injury. In one report, ultrasonographic evidence of an increase in renal size up to 200% of normal size, due to inflammation and edema.[23] In one study, it was revealed by USG that increase the width of the kidney was greater than other dimensions.[7] Gallium scintigraphy has been used for over 33 years based upon the binding of gallium to lactoferrin either expressed on the surfaces of inflammatory cells or produced in the interstitium. So, gallium scanning shows the interstitium enhancement, which is compared with the spine. It has a limited role due to low sensitivity and specificity i.e., 50% to 60%. Lower specificity is due to the positive scan and is also observed in other inflammatory diseases besides TIN likely glomerulonephritis, atheroemboli, and pyelonephritis. One strong indication of a gallium scan is when a renal biopsy is contraindicated or refusal by patients.[19] PET scan can also be used in the diagnosis of biopsy-proven acute TIN. In some cases, even PET scans were found to be positive for gallium scan negative patients.

Blood Testing

The most significant manifestation of renal failure in the TIN is an increased level of blood urea nitrogen and serum creatinine. The diagnosis could be considered initially when patients develop a rise in serum creatinine levels.[17] Electrolyte and acid-base disturbances essentially hyperkalemic, hyperchloremic metabolic acidosis that is out of proportion with the degree of kidney failure, raising clue for associated tubulointerstitial injury.[23][24] Increased eosinophils level is most commonly linked with drug-induced TIN principally methicillin beta-lactam (80%) but rare with other non-beta-lactam drugs. Still, sadly, eosinophilia is not sensitive because it may occur in other diseases such as vasculitis, malignancies, eosinophilic leukemia, and cholesterol emboli syndrome. Elevated serum IgE level also implies the allergic conditions, basically drug-induced TIN. In addition, decreased erythropoietin synthesis due to tubular cell injury and erythropoietin resistance as a result of undergoing inflammation leads to anemia. Elevated serum Erythrocyte Sedimentation Rate (ESR) or C-reactive proteins hints the inflammatory process. Other parameters, such as abnormal liver function tests signal the associated drug-induced hepatitis, Fanconi syndrome, salt-wasting nephropathy, and urine concentrating defects, are rarely illustrated.[19]

Urine Analysis and Microscopy

Urine analysis is one of the most commonly used tests and provides a helpful clue in the diagnosis of TIN. Positive proteinuria in dipstick test and microscopic or macroscopic hematuria is associated with drug-induced TIN in less than 50% of cases, but about 90% in beta-lactam antibiotics induced TIN. Urine leukocytes are present in almost all patients with methicillin induced TIN but less common with other antibiotics. Esinophiluria (Wright or Hansel stain) is present in the drug-induced acute TIN but not sensitive and specific due to present in other conditions too.[17] Visualization of urine microscopy shows WBC casts in the absence of pyelonephritis. Tubular cells injury by inflammatory process manifests as hyaline and granular casts in around 80% of drug-induced acute TIN, and surprisingly RBC casts and WBC casts are seen on only 26% and 14% respectively. Hence, clinicians should not exclude acute TIN as a cause of AKI on the basis of the presence or absence of pyuria or WBC casts.[1][19] Evaluation of urine chemistry and electrolytes, osmolality, fractional excretion of sodium does not aid in diagnostic purposes.
Diagnosis and monitoring of disease activity are helped by urinary biomarkers, for instance, monocyte chemotactic peptide-1 (MCP-1), alpha1-microglobulin (A1M), and beta2- microglobulin (B2M).[1] These are low molecular proteins passed in urine suggests tubular injury and interstitial pathology. One study with urinary biomarkers concluded that B2M has higher sensitivity and specificity than A1M.[25] MCP-1 is usually observed in the drug-induced TIN.[1]

Treatment / Management

It is essential to have high clinical suspicion to eliminate causative agents and treat associated systemic disorders. Treatment is supported by the clinician's experience, study series, case reports, and randomized control trials. Therefore, treatment should be according to underlying etiology. Discontinuation of drugs is the first line of treatment in drug-induced TIN with alternative drug administration to treat infections that often lead to the reversal of renal injury.[17] However, renal damage may not be completely reversible depending on the duration of exposure of offenders, degree of tubular atrophy, and severity of interstitial fibrosis. Corticosteroids have been the mainstay treatment against the inflammatory process, which reduces fibrosis, but randomized control trial poorly supports the corticosteroid therapy for long term renal survival. Limited large retrospective series and controlled trials show inconsistency over the benefits of corticosteroid therapy. Therefore it may be preserved for the cases with severe renal failure where dialysis is imminent and renal functions deteriorate despite the removal of offending agents. A multicenter retrospective study performed revealed improvement in renal function in cases of early prompt corticosteroid administration after diagnosis and removal of drugs. It showed complete recovery in about 54% of people that received steroid treatment as compared to only 33% with no steroid treatment. Also, the need for chronic dialysis is more i.e., up to 44% in the no corticosteroid treatment group compared to only 4% in the steroid-treated patient group.[26] Another retrospective study demonstrated a comparison between non-steroid conservative therapy and steroid therapy did not show significant differences in the outcome on the basis of evaluation and monitoring of serum creatine level follow-up at 1, 6, and 12 months.[5] In contrast, a prospective study of corticosteroid therapy in children having idiopathic or TIN and uveitis syndrome produced prompt recovery of TIN, especially in more severe disease. However, renal function did not vary significantly in control and study groups after 6 months of follow-up.[27] Whereas, patients who did not receive steroids immediately after removal of culprit have higher baseline creatine levels. The most widely used regimen is methylprednisolone (IV 250-500 mg), followed by prednisone 1 mg/kg/day.[28]

The role of mycophenolate mofetil has been demonstrated in recent studies.[2] It is mainly useful in steroid-resistant cases, and steroid contraindicated cases. Vancomycin-induced granuloma interstitial nephritis was found to be generally refractory to steroid so, treated with cyclosporine and mycophenolate mofetil showed amelioration in renal function.[29]

Corticosteroids and other immunosuppressants, i.e., azathioprine, are indicated mainly in cases associated with systemic inflammatory and autoimmune diseases such as Sjögren syndrome, sarcoidosis, SLE, TIN with uveitis, and other granulomatous diseases. A retrospective study advocated improved prognosis of corticosteroid use in granulomatous interstitial nephritis regardless of the extent of fibrosis and inflammation on biopsy.[30] Another published case report proposed that corticosteroid treatment in cases of mild tubulointerstitial fibrosis has a better response in the granulomatous TIN. Primarily, corticosteroids have an enormous benefit over sarcoidosis and TIN with uveitis; unfortunately, it has more chances of relapse after withdrawal and needs a longer duration of therapy as compared to the drug-induced TIN.[28] Additionally, cases associated with sarcoidosis can be treated with steroid-sparing agents such as infliximab [31] and azathioprine. IgG4-associated TIN responds well to corticosteroid treatment though the relapse rate after discontinuation is high.[2]

Management of infection-related TIN is the treatment of underlying infections with convenient antibiotics. Besides, there are no other well-described treatment methods. Corticosteroids have little or no role in an infection-related TIN.[28] In TIN with uveitis, uveitis is treated with topical cycloplegics and corticosteroids, which gives around 50% of positive response.[32][33][34] Viral related transplant rejection is managed by reducing the immunosuppressants and specific retroviral drugs.[35]

Supportive and conservative care should be provided to those patients whose adverse effects of medications and severe renal failure. Fluid and electrolyte management, avoid volume depletion or overload, adequate hydration, symptomatic relief of fever, rash and systemic symptoms, avoidance of nephrotic drugs and drugs that impair renal blood flow, supportive dialysis, etc.[22]

Differential Diagnosis

Clinical presentations and laboratory results of TIN are not specific rather similar in most of the diseases of the kidney, causing AKI and renal insufficiency. So differentials of TIN includes all those causes of AKI. Thus, clinicians use different diagnostic tests, i.e., biopsy, imaging, etc. to differentiate the TIN from AKI because therapeutic interventions are different according to the various causes of AKI. While assessing the suspected tubulointerstitial nephritis in patients with renal insufficiency, the following problems should be considered:

Acute Tubular Necrosis

It is the most common cause of acute renal failure characterized by tubular cells necrosis insulted from ischemia, toxins such as aminoglycosides, heavy metal, urate, radiocontrast dye, and ethylene glycol. Clinical pictures like oliguria, metabolic acidosis, elevated BUN, and creatinine, electrolyte imbalance are similar to that of TIN.


Atheroemboli (also called cholesterol crystal emboli) should be considered in patients with predominance urinary WBC and RBC casts. Atheroemboli may also present with skin rashes, eosinophiluria, eosinophilia, but skin eruptions are livedo reticularis and digits infarcts rather diffuse maculopapular type in TIN. History of endovascular diseases, old age, obesity helps to figure out atheroemboli.[36]


It is a wide range of glomerular inflammatory immune-mediated diseases, also involving other compartments of the kidney. It ultimately leads to renal insufficiency, and renal failure as TIN. common presentations of glomerulonephritis are similar to TIN, such as proteinuria, oliguria, RBC casts, so visualization of glomeruli and immune complex deposition in light and electron microscopy helps to differentiate different types glomerulonephritis each other and from the TIN.[37]

Vascular Injury

Different cardiovascular insults likely renal artery stenosis, cardiac failure, vasculitis, reduced blood flow due to afferent arteriolar constriction by inhibited prostaglandin synthesis in NSAIDs user, reduced efferent arteriolar tone by ACE inhibitors, etc. are the common causes of AKI that clinically simulate the TIN.

Urinary Tract Obstruction (UTO)

 UTO is the postrenal cause of acute renal failure, obstruction commonly by various renal stones, tumors, strictures. In patients, sometimes presenting anuria or absence of sediment should consider the obstruction as a differential diagnosis. In such patients, imaging helps to distinguish the obstruction from other causes of AKI. Obstruction is the favorable nidus for infection, which drives the ascending infection and, thus, the pyelonephritis sooner or later. Sterile pyuria, WBC casts, leukocytosis, positive dipstick test for leukocyte esterase, flank pain are the common manifestations.[38] 


Prognosis basically depends upon the cause of TIN, timing of therapy, renal function, previous offending agent, and time of removal of the cause. Chronicity portends worse outcomes, and early identification and removal of the cause improve the renal outcomes, and early treatment expedites prognosis. In general, the drug-induced TIN has a good prognosis because of potential partial recovery of the kidney occurs.[17] On the contrary, granulomatous TIN has a poorer prognosis.[28] Prolonged low molecular proteinuria such as A1M, B1M, and MCP-1 is a marker for poor prognosis and decreased glomerular filtration rate.[1] Long term prognosis is usually encouraging with full kidney recovery.[18] Adverse prognostic factors include diffuse inflammation versus the better outcomes in patchy inflammation. High inflammatory cells, extensive fibrosis has a declining prognosis in recovery. Patients who halt the offending medication within two weeks of the commencement are more inclined to recover nearly baseline function as compared to those taking medication for three or more weeks.[22]


Elderly patients are more vulnerable to complications. Delay in diagnosis and treatment worsens the condition. Renal insufficiency is a common manifestation that ultimately progresses to end-stage renal disease. The inflammatory interstitium is completely replaced by fibrosis, and severe degeneration of tubular epithelial cells induces irreversible renal impairment necessitating early renal dialysis and renal transplantation. Initially, glomeruli are usually spared, but later on, glomeruli are also involved. Damage of glomeruli provokes the hyperfiltration of proteins, glucose, Blood cells, and other essential components of blood, and the insufficiency of reabsorption from damaged renal tubular cells causes an excessive loss in urine—body electrolytes and acid-base imbalance consequences the hypokalemic metabolic acidosis. The involvement of proximal tubules, especially in a TIN with uveitis heightens the chances of glycosuria, hyperphosphatemia, hyperuricosuria, proximal renal tubular acidosis, aminoaciduria, proximal renal tubular acidosis, and kaliuresis which is described as Fanconi syndrome.[39][40][41] A report of 39-year old male presented with multiple bone pain, polydipsia, and polyuria due to loss of phosphate in urine evident with hypophosphatemic osteomalacia and osteoporosis in TIN associated Sjögren syndrome concluded bone disorder as one of the rare complications.[42]

Some cases of TIN as a result of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis transform to necrotizing crescentic glomerulonephritis when corticosteroid therapy is delayed.[43] The involvement of proximal renal tubular cells due to inflammation or infection results in either decreased synthesis or hyporesponsiveness of erythropoietin by injured cells leads to decreased stimulation of bone marrow hematopoietic stem cells for RBCs production causes anemia.[19] Frequent use of NSAIDs may trigger the progression of nephrotic syndrome. Succeeding nephrotic and nephritic syndrome in long-standing cases of TIN presents with pitting edema as a result of hypoalbuminemia, risk of infection due to hypogammaglobulinemia, hyperlipidemia, periorbital edema, hematuria, and azotemia. Scarce but still noted, induced arterial hypertension due to sodium retention in tubulointerstitial inflammation by increased angiotensin II activity and increased oxidative stress.[13][44] Increased angiotensin concentration, as well as activity, is by virtue of its expression in inflammatory and renal tubular cells, change the hemodynamic status, and oxidative stress causes vasoconstriction.[45][46] Lupus nephritis related persistent arterial hypertension is also conspicuous in about two-thirds of cases.[44]

Deterrence and Patient Education

Information provided to patients about the disease and course of treatment should be understandable. Well educated patients who want in-depth information are provided with more sophisticated and detailed notes about the whole procedures. Every patient has curiosity and right to know about their disease. This helps to decrease the communication gap between clinicians and patients. Patient education also assists the patients to clear their doubts and motivate themselves to tackle the problems. Patients become optimistic and compliant with routine therapy and also cooperate with clinicians. So, health education has always been a high priority. Briefing about the disease, signs and symptoms, treatment options, side effects, and complications of the disease enables the patients to make appropriate decisions and alert them and present early in the clinic. Preventive measures, any diagnostic tests, consent before invasive interventions come under patient education. Afterall it improves the whole healthcare system.

Enhancing Healthcare Team Outcomes

In most of the countries enhanced healthcare system is still unavailable. The interprofessional healthcare approach has always been highly appreciated and desired, which brings about a better outcome. Developed countries are already working through multiple healthcare teams to make precise diagnoses and imply relevant treatment. The need for different professionals depends upon the complexity of the disease process. Tubulointerstitial nephritis has a wide range of etiology which needs clinicians from different specializations such as nephrologists, urologists, infectious disease experts, ophthalmologists in cases of TIN with uveitis, and pulmonologists.[32] Diagnostics approaches can be done effectively with the help of histopathologists, radiologists, lab technicians, microbiologists. Skin rashes in drug-induced hypersensitivity are feasible with the help of dermatologists' opinion. Nursing care of the patients is an inseparable entity in every hospitalized patient, and pharmacists provide drug education and review side effects. Surgeons have their role in biopsy and chronic kidney disease in renal transplantation with the aid of anesthetists. In this way, the comprehensive healthcare team gives better results.


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