Tubulointerstitial nephritis in children and adolescents.

The tubulointerstitial compartment comprises most of the kidney parenchyma. Inflammation in this compartment (tubulointerstitial nephritis-TIN) can be acute and resolves if the offending factor is withdrawn or may enter a chronic process leading to irreversible kidney damage. Etiologic factors differ, including different exposures, infections, and autoimmune and genetic tendency, and the initial damage can be acute, recurrent, or permanent, determining whether the acute inflammatory process will lead to complete healing or to a chronic course of inflammation leading to fibrosis. Clinical and laboratory findings of TIN are often nonspecific, which may lead to delayed diagnosis and a poorer clinical outcome. We provide a general review of TIN, with special mention of the molecular pathophysiological mechanisms of the associated kidney damage.

Chronic Tubulointerstitial Nephritis and Peripheral Neuropathy Probably Due to Pantoprazole Mimicking Systemic Disease.

The coexistence of peripheral neuropathy and chronic tubulointerstitial nephritis in a patient can be secondary to various diseases including-connective tissue disorders, sarcoidosis, IgG4-related disease, heavy metal poisoning, plasma cell dyscrasias, and drugs. A 70-year old woman was admitted with fatigue for 4 months and numbness of both lower limbs for 6 months. She had antral gastritis and was on treatment with pantoprazole for 1 year. On evaluation, she had peripheral neuropathy and chronic tubulointerstitial nephritis which was suspected to be secondary to pantoprazole after ruling out other causes. We present a patient with multiple complications (peripheral neuropathy and chronic tubulointerstitial nephritis) likely associated with pantoprazole which was not reported in the literature previously to the best of our knowledge.

Combination Cyclophosphamide/Glucocorticoids Provide Better Tolerability and Outcomes versus Glucocorticoids Alone in Patients with Sjogren's Associated Chronic Interstitial Nephritis.

BACKGROUND: Steroid therapy has become an effective option for patients with primary Sjogren's syndrome with tubulointerstitial nephritis (TIN), while the use of cytotoxic agents is still debated. Our study aimed to compare the clinical outcomes of patients treated with cyclophosphamide (CTX) combined with glucocorticoids with those of patients treated with glucocorticoids alone. METHODS: All patients with primary Sjogren's syndrome with chronic TIN admitted to the Division of Nephrology, Ruijin Hospital, from January 1, 2002, to April 30, 2016, and treated with steroids alone or combined with CTX were included. The immunological prognosis, improvements of renal function, and acquired tubular defects of the patients were retrospectively compared between the 2 therapeutic groups. RESULTS: A total of 70 cases were included. Of these, 36 were diagnosed by renal biopsy. A total of 56 patients were treated with glucocorticoids alone, while 14 patients received glucocorticoids combined with CTX. There were no significant differences in clinical characteristics and laboratory parameters between the 2 therapeutic groups at baseline. Compared with patients in the steroid group, patients in the CTX group showed better estimated glomerular filtration rate (eGFR) improvement (21.35 ± 19.63 vs. 2.72 ± 19.11 mL/min/1.73 m2, p = 0.006) but a similar decline in immunoglobulin G (IgG; 450 [interquartile range, IQR 910] vs.176 [IQR 1,910] mg/dL, p = 0.93) at 12 months of follow-up. CTX therapy was associated with better eGFR improvement (ß = 12.96 [2.95-22.97]) even after adjusting for dry mouth, anti-Sjögren's-syndrome-related antigen A and anti-Sjögren's-syndrome-related antigen B positivity, hemoglobin, initial steroid dose, and baseline eGFR by linear regression analyses. Subgroup analyses revealed that the beneficial effects of CTX therapy on renal function were only observed in patients with baseline IgG ≥1,560 mg/dL or eGFR <90 mL/min/1.73 m2. The urine α1-microglobulin improvement was better in the CTX group than in the steroid group at 12 months of follow-up (ß = 1.29, 95% CI 0.56-2.02, p = 0.001). CONCLUSIONS: CTX therapy is suggested for primary Sjogren's syndrome patients with chronic TIN, especially those with higher IgG levels and abnormal renal function at baseline.

Coexistence of Diffuse Large B-Cell Lymphoma With Chronic Tubulointerstitial Nephritis: A Case Review and Pathophysiology.

There is an association between lymphomas and kidney disease with renal abnormalities found both in patients with direct infiltration by lymphoma as well as in patients without gross or microscopic evidence of renal involvement. Multiple mechanisms to explain the link between lymphomas and renal disease have been proposed, ranging from direct renal metastasis by the lymphoma to chemokine signaling pathways. In addition, there is a correlation between certain genetic mutations and an increased risk of lymphoma metastasizing to other organs. We present a case of a 41-year-old male who passed away due to end-stage kidney disease and was found on autopsy to have chronic tubulointerstitial nephritis and diffuse large B-cell lymphoma (DLBCL) without direct renal involvement by the lymphoma. The patient had been previously healthy with no significant prior medical history, NSAID, or other contributory medication use of note with the only presenting symptom being renal failure. Only upon autopsy was DLBCL discovered throughout the abdomen with no direct lymphoma involvement evident in the kidneys. To the author's knowledge, this is one of the few reported cases of DLBCL in English literature without renal infiltration in which the presenting symptom and cause of death was renal dysfunction. Several mechanisms have been theorized for how lymphomas can lead to kidney damage without direct metastasizes; however, more research still needs to be done to better understand the underlying etiology. Given the rarity and the lack of direct infiltration of lymphoma into the kidneys in this patient, we hope reporting this case will allow further advancements in this field of study as well as more comprehensive management.

New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene.

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene. METHODS: Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations. RESULTS: Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSION: To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.

Clinical Approach to Diagnosing Acute and Chronic Tubulointerstitial Disease.

Tubulointerstitial diseases are a relatively common cause of acute and/or chronic kidney disease. Acute tubulointerstitial nephritis (ATIN) most commonly develops in patients exposed to various medications; however, it can occur from infections, autoimmune and systemic diseases, environmental exposures, and some idiopathic causes. Chronic tubulointerstitial nephritis may develop in patients with previous ATIN or may be the initial manifestation of an autoimmune, systemic, environmental, or metabolic process. It can be challenging for clinicians to differentiate the various causes of acute and chronic kidney disease. In particular, distinguishing ATIN from other causes of acute kidney injury, such as acute tubular necrosis or a rapidly progressive glomerulonephritis, is important as treatment and prognosis are often quite different. To this end, clinicians use clinical assessment, certain laboratory data, and various imaging tests to make a diagnosis. Unfortunately, most of these tests are insufficient for this purpose. As a result, kidney biopsy is often required to accurately diagnose ATIN and guide management. For chronic tubulointerstitial nephritis, kidney biopsy is needed less often as available therapies for this entity, with a few exceptions, are limited and primarily supportive.

Chronic tubulointerstitial nephritis in a solitary kidney of a child with Noonan syndrome.

Noonan syndrome is a genetic disorder with involvement of many organ systems; facial dysmorphism and cardiovascular defects being the common abnormalities. Renal involvement is uncommon and abnormalities of the genitourinary system are usually limited to structural anomalies and cryptorchidism. We report a case of Noonan syndrome with chronic tubulointerstitial nephritis in a solitary kidney.