A case of acute poststreptococcal glomerulonephritis complicated by interstitial nephritis related to streptococcal pyrogenic exotoxin B.

This paper presents the case of a patient who developed acute kidney injury and nephrotic syndrome following streptococcal cutaneous infection. He presented with microhematuria, severe proteinuria and systemic edema 5 days after infection. Blood examination showed elevated creatinine level, hypocomplementemia, and elevated anti-streptolysin O level. Renal biopsy revealed endocapillary proliferative glomerulonephritis with tubulointerstitial nephritis (TIN). Immunofluorescence revealed C3-dominant glomerular staining, while electron microscopy showed hump-shaped subepithelial deposits. The patient was therefore diagnosed with poststreptococcal glomerulonephritis. The unique histological feature was C3 deposition in the tubular basement membrane (TBM), in which we detected streptococcal pyrogenic exotoxin B (SpeB), a nephritogenic antigen produced by streptococci. No nephritis-associated plasmin receptor or plasmin activity was evident in the TBM. These nephritogenic antigens and upregulation of plasmin activity were observed in glomeruli. This case suggests that TIN after poststreptococcal infection might be partially attributable to SpeB toxicity.

Simultaneous subacute interstitial nephritis and anticoagulant-related nephropathy related to novel oral anticoagulants use.

Introduction: Interstitial nephritis related to novel oral anticoagulants was only reported in sporadic case reports and none was accompanied by anticoagulants related nephropathy (ARN).Case Report: We presented here a case of biopsy-proven subacute interstitial nephritis (SubAIN) accompanied by ARN after oral dabigatran to alarm clinicians. This case manifested with gross hematuria, acute kidney injury, slightly prolonged thrombin time, moderate anemia, moderate proteinuria, a large quantity of intratubular hemoglobin casts confirmed by hemoglobin antibody immunohistochemical staining which presumed to occur around 1 week after dabigatran and subacute interstitial nephritis accompanied by focal proliferative glomerulonephritis. Serum creatinine level did not continue to elevate after discontinuation of the oral anticoagulant. With the subsequent supportive therapy, it decreased to some extent then reduced to normal with the help of prednisone (half of the full dose).Conclusions: When we came across a patient who manifested as hematuria or acute kidney injury with a history of anticoagulants usage, we should think of ARN and pay more attention on history collection. Secondly, subacute interstitial nephritis may coexist with ARN. Thirdly, hemoglobin immunohistochemical staining may be helpful to make it clear whether the intra-tubular protein casts came from red blood cells. In addition, for those patients who may have decreased kidney function, anticoagulants dose should be reduced to prevent the occurrence of ARN.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Accompanied by IgG4-Tubulointerstitial Nephritis with Underlying Sjögren Syndrome: A Case Report and Review of Literature.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune multisystemic diseases characterized by necrotizing inflammation of small vessels and the presence of circulating ANCA. The prevalence of overlap AAV with other autoimmune diseases was low. CASE REPORT: We report a case of a 54-year-old woman who presented with a 20-year-history of sicca symptoms, the presence of anti-Ro/SS-A, anti-La/SS-B antibodies, myeloperoxidase -ANCA (MPO-ANCA), significant increase of serum IgG4 level, microscopic hematuria, non-nephrotic proteinuria, and progressive renal dysfunction. A renal biopsy showed pauci-immune necrotizing glomerulonephritis with crescents with severe tubulointerstitial nephritis (TIN) which shows extensive infiltration of IgG4-positive plasma cells. Considering these findings and the clinical course, the disease was considered more likely to be MPO-ANCA-associated vasculitis accompanied by IgG4-TIN with underlying primary Sjögren syndrome (pSS). CONCLUSION: This report shows a possible unusual disease overlap of MPO-ANCA-associated vasculitis and IgG4-TIN with underlying pSS.

Acute interstitial nephritis and nephrogenic diabetes insipidus following treatment with sulfamethoxazole-trimethoprim and temozolomide.

We report a case of acute interstitial nephritis with associated nephrogenic diabetes insipidus in a patient treated with temozolomide and sulfamethoxazole-trimethoprim for glioblastoma multiforme. Kidney biopsy demonstrated focal tubulointerstitial change with tubular dilatation, epithelial change and interstitial inflammation. The patient's kidney function improved with cessation of sulfamethoxazole-trimethoprim and treatment with hydrochlorothiazide for nephrogenic diabetes insipidus. Recommencement of temozolomide did not result in further deterioration in kidney function. In this case report, we discuss the novel association between sulfamethoxazole-trimethoprim-induced acute interstitial nephritis and nephrogenic diabetes insipidus, and suggest possible mechanisms involved.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

Acute Interstitial Nephritis and Acute Tubular Injury Due to a Transdermal Loxoprofen Patch.

A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.

A rare case of cephalexin-induced acute interstitial nephritis with hypokalemic periodic paralysis.

Drug-induced acute interstitial nephritis (AIN) is often encountered in clinical practice. Cephalexin is a first-generation cephalosporin with antimicrobial sensitivity ranging from Gram-positive to Gram-negative organisms. Cephalexin-induced AIN presenting with hypokalemic periodic paralysis (HPP) has been rarely reported. A 34-year-old female with recent history of oral cephalexin intake presented with acute onset paraplegia with deranged renal parameters and hypokalemia. She was treated conservatively with mechanical ventilator support. HPP could be a rare clinical presentation for cephalexin-induced AIN.

Primary Sjögren syndrome-associated acute interstitial nephritis and type 3 renal tubular acidosis in a patient with thin basement membrane nephropathy: A case report.

INTRODUCTION: The kidney is one of the common extraglandular sites involved in primary Sjögren syndrome (pSS), with chronic tubulointerstitial nephritis (TIN) the most common pathology type. Renal involvement in pSS often presents as chronic TIN accompanied by type 1 or 2 renal tubular acidosis (RTA). Description of renal involvement as acute TIN with type III RTA in pSS has been rarely reported. PATIENT CONCERNS: A 37-year-old woman was admitted with complaints of dry mouth, dry eyes, and progressive muscle weakness for 17 months. Two months before admission, the patient had a blood potassium level of 1.7 mmol/L. DIAGNOSIS: Further tests confirmed pSS and type III RTA. Renal biopsy demonstrated acute TIN and thin basement membrane nephropathy (TBMN). INTERVENTIONS: Full-dose corticosteroid (1 mg/kg/day) and cyclophosphamide (100 mg/day) were applied. OUTCOMES: The creatinine levels of the patient decreased 0.28 mg/dL (1.18-0.90 mg/dL) during 3-month follow-up. CONCLUSIONS: We reported a patient with pSS-associated kidney injury, presenting as acute TIN with type 3 RTA and TBMN. This case increases the awareness of a rare manifestation of pSS-associated kidney injury. In pSS-associated acute TIN, cyclophosphamide combined with full-dose corticosteroids may achieve good outcomes.

Nephrological disorders and neurological involvement in pediatric primary Sjogren syndrome:a case report and review of literature.

BACKGROUND: Sjögren syndrome (SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic. CASE PRESENTATION: A 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B (anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient's medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria. CONCLUSIONS: Nephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications.

IgA Nephropathy Concomitant With Karyomegalic Interstitial Nephritis.

Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis characterized by the deposition of IgA in glomerular mesangium. Karyomegalic interstitial nephritis (KIN) is a rare interstitial nephritis with potential hereditary factors. IgA nephropathy concomitant with KIN has not yet been reported. Herein, we describe the clinical course, ultrasonic images and gastrointestinal endoscopy findings of a 28-year-old-male patient with IgA nephropathy with KIN. The pathologic examination of the renal biopsy specimen demonstrated mild mesangial proliferative IgA nephropathy with KIN. Molecular genetic testing detected an abnormality in FAN1 gene. The heterozygous mutation was present on chromosome 15q13.3. However, IgA nephropathy with KIN is a rare disorder, and its pathogenesis is yet to be clarified.

Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. METHODS: We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. RESULTS: The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1-2) or λ-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1-2 and as λ-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. CONCLUSIONS: We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.

Case report: a 58 -year -old man with small kidneys and elevated liver enzymes.

BACKGROUND: The conjunction of hepatitis and renal disease can be seen in several clinical context, including karyomegalic nephritis (KIN). Karyomegalic nephritis (KIN) is a rare genetic disease, with less than 50 cases reported, which incidence is probably underestimated. We report here an unusual case presentation of KIN with obtention of several organ biopsies and a novel mutation leading to the disease. CASE PRESENTATION: A 58 year old Caucasian without relevant family history presents with advanced chronic kidney disease, elevated liver enzymes and recurrent pulmonary infection. Familial history was negative. Renal biopsy revealed a chronic tubulo-intertsitial nephritis with enlarged and irregular hyperchromatic nuclei. Karyomegalic nephritis (KIN) was confirmed by genetic testing with a non-sense mutation and a deletion in the Fanconi anemia associated nuclease 1 (FAN1) gene. CONCLUSIONS: KIN is rare disease to be suspected in the presence of renal disease, biological hepatitis and recurrent pulmonary infections, even without a familial history. Diagnosis of this condition is crucial to perform family screening, avoid progression factors, and adapt post transplantation immunosuppression. Finally, avoiding familial heterozygote donors appears of major importance in this condition.

Acute tubulointerstitial nephritis in children- a retrospective case series in a UK tertiary paediatric centre.

BACKGROUND: Acute tubulointerstitial nephritis (AIN) is an uncommon cause of acute kidney injury in children, accounting for less than 10% of cases. There is limited information regarding the range of underlying diagnoses and how these may differ geographically. We undertook a retrospective case note review of consecutive cases of biopsy-proven AIN, presenting to a single UK tertiary paediatric centre, to describe the range of AIN in our caseload, define key characteristics and response to treatment, with the aim of informing paediatric nephrology practice. METHODS: Cases were identified retrospectively from departmental records. Data extracted included demographics, presenting clinical and biochemical features, renal biopsy histology, treatment and follow-up. RESULTS: Ten cases were identified over 8 years (2007-2014). Age range 6-16 years. Male:Female ratio 1:9. Final diagnoses included 6 tubulointerstitial nephritis and uveitis syndrome (TINU), 2 idiopathic, 1 sarcoidosis, 1 child with Streptococcal disease. Of the TINU cases, timing of eye symptoms varied in relation to AIN presentation. Cases had a varied investigative work-up. Median presenting plasma creatinine was 303 µmol/l (range 152-932 µmol/l). Renal function improved spontaneously in 1 idiopathic case and improved with antimicrobial treatment in a child with Streptococcal disease. Eight cases received immunosuppressive treatment with intravenous methylprednisolone (approximately 10 mg/kg for 3-5 days) and / or oral prednisolone (1-2 mg/kg initially, reducing over 7-28 days). At 1 month, median creatinine had fallen to 91 µmol/l (range 41-120 µmol/l) with median eGFR 61 ml/min/1.73m2 (range 51-103 ml/min/1.73m2). At last follow-up (median 18.5 months, range 2-70 months), median creatinine was 71 µmol/l (range 47-90 µmol/l) with median eGFR 80 ml/min/1.73m2, range 63 to 101 ml/min/1.73m2). Two patients received antihypertensives at diagnosis and 1 further patient at 1 month follow-up. Eight patients received electrolyte supplementation. Median time to discontinuing electrolyte supplementation was 3.5 months (range 1-12 months). CONCLUSION: To our knowledge, this is the only contemporary UK case series of biopsy-proven AIN in children. Our population has a high proportion of TINU. Treatment was accompanied by improvement of renal function, however 7/10 patients had an eGFR < 90 ml/min/1.73m2 at last follow-up. We suggest a standardised investigative work-up and recommend long-term follow-up.

Drug-induced tubulointerstitial nephritis: hypersensitivity and necroinflammatory pathways.

More than 250 drugs carry a small but important dose-independent risk of initiating a delayed-type hypersensitivity reaction that leads to acute tubulointerstitial nephritis (TIN). Clinical manifestations are often non-specific, making epidemiological studies challenging. In severe cases, if cessation of the offending drug is not followed by a prompt improvement in renal function, corticosteroid therapy appears to enhance renal recovery rates. Other drugs, classified as potential nephrotoxins, may induce dose-dependent acute tubular necrosis. Studies over the past decade have identified a unique form of tubular cell death called "necroptosis" that is accompanied by a specific and significant interstitial inflammatory response to certain insults, including some nephrotoxins. Insights into the molecular basis of this necroinflammatory pathway have emerged. There is still a paucity of pediatric data on these two distinct types of drug-induced TIN. Early recognition is essential to minimize the risk of chronic kidney damage.

Renal Effects after Pembrolizumab Treatment for Non-small Cell Lung Carcinoma.

Immune checkpoint inhibitors (CPIs), including pembrolizumab, are becoming common oncological treatments. CPIs have been associated with a significant risk of developing immune-related adverse events (irAEs), such as nephritis and interstitial nephritis. However, the occurrence of glomerulonephritis has only rarely been reported. We herein present the case of a 75-year-old woman with non-small cell lung carcinoma (NSCLC) who developed proteinuria and microscopic hematuria during treatment with pembrolizumab. Renal biopsy revealed tubulointerstitial nephritis and IgA nephropathy. Considering that a urinalysis showed no abnormality before treatment, the condition might have been induced by pembrolizumab. In this report, we focus on the correct diagnosis and management of renal irAEs, which remain controversial.

Acute tubulointerstitial nephritis with germinal centers in antineutrophil cytoplasmic antibody-associated vasculitis: A case report and literature review.

RATIONALE: Occasionally, tubulointerstitial lesions can be found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, significantly isolated tubulointerstitial nephritis (TIN) with germinal centers is rare. PATIENT CONCERNS: A 17-year-old Chinese Han patient showed rapidly progressive glomerulonephritis, anuria, and serum creatinine of 19.4 mg/dL. DIAGNOSIS: He had positive ANCA targeting myeloperoxidase (55.0 RU/mL). The renal biopsy showed crescent formation in 100% of glomeruli. Of special note, the glomerular crescents were surrounded by granulomatous inflammation, extensive tubular destruction or disappearance, and massive interstitial infiltration. A diagnosis of AAV was thus made with the involved organ restricted to the kidney. INTERVENTIONS: The patient underwent 7 rounds of plasmapheresis, 3 pulses of methylprednisolone therapy (500 mg per pulse), and oral prednisolone (50 mg/d). Rituximab (500 mg) was used after the plasma exchange treatment. OUTCOMES: ANCA was negative, while anti-modified C-reactive protein (anti-mCRP) antibodies remained positive. The patient was dependent on hemodialysis. We found anti-mCRP antibody in the serum of the patient, with the major epitope on amino acids 35 to 47 of mCRP. LESSONS: We proposed that the anti-mCRP antibody might play an important role in this case of acute TIN in AAV.

A novel disease-causing mutation in the Renin gene in a Tunisian family with autosomal dominant tubulointerstitial kidney disease.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare group of disease that affect the tubules of the kidney. There are 4 known subtypes of ADTKD classified based on causative genes and clinical features. In our study, we aimed to identify the causative subtypes of ADTKD in a Tunisian ADTKD family (3 affected members), in whom standard nephrological diagnosis did not provide clear subtype of ADTKD, until genetic testing was performed. Sanger sequencing was performed for UMOD, HNF1ß and REN genes. Mutational analysis allowed us to detect a heterozygous mutation in the REN gene: c.1172C > G, (p.T391R) in exon 10. In silico analyses predicted that the novel likely pathogenic mutation affect protein stability and 3D structure. Our study highlights the importance of establishing a genetic diagnosis to identify the subtype of ADTKD for better patient care. To the best of our knowledge, we report here a first Tunisian ADTKD-REN family.