Effect of steroid pulses in severe BK virus allograft nephropathy with extensive interstitial inflammation.

INTRODUCTION: As there is no specific antiviral treatment currently available for BK polyomavirus associated nephropathy (BKVAN), its management relies on immunosuppression reduction in kidney transplant patients. Data on efficacy of steroid pulses in this indication are lacking. METHODS: We performed a retrospective monocenter study on 64 patients diagnosed with biopsy-proven BKVAN. Patients within the "pulse group" (n = 37) received IV methylprednisolone 10 mg/kg 3 days consecutively. In the "low dose" steroid group (n = 27), patients were continued oral prednisone 5 mg daily. RESULTS: Mean follow up was 78 months in the steroid pulse group and 56 months in the low dose group (p = 0.15). Mean eGFR values at diagnosis were comparable, as well as other demographic characteristics. Mean BK plasma viral load was higher in "pulse" than in "low dose" steroid group. Pulse group had higher inflammation and tubulitis (p < 0.05). Graft loss reached 57% in the "pulse" group versus 41% in the "low dose" group, p = 0.20. Rejection events were similar. No major adverse event was statistically associated with steroid pulse, including infections, cancer, and de novo diabetes. CONCLUSION: No significant differences were found in the evolution of both groups of patients, despite patients receiving "pulse" steroids were identified as the most severe sharing higher BK viral load and more frequent active lesions on histology.

Distinct developmental reprogramming footprint of macrophages during acute kidney injury across species.

Acute kidney injury (AKI) is a common finding in hospitalized patients, particularly those who are critically ill. The development of AKI is associated with several adverse outcomes including mortality, morbidity, progression to chronic kidney disease, and an increase in healthcare expenditure. Despite the well-established negative impact of AKI and rigorous efforts to better define, identify, and implement targeted therapies, the overall approach to the treatment of AKI continues to principally encompass supportive measures. This enduring challenge is primarily due to the heterogeneous nature of insults that activate many independent and overlapping molecular pathways. Consequently, it is evident that the identification of common mechanisms that mediate the pathogenesis of AKI, independent of etiology and engaged pathophysiological pathways, is of paramount importance and could lead to the identification of novel therapeutic targets. To better distinguish the commonly modulated mechanisms of AKI, we explored the transcriptional characteristics of human kidney biopsies from patients with acute tubular necrosis (ATN), and acute interstitial nephritis (AIN) using a NanoString inflammation panel. Subsequently, we used publicly available single-cell transcriptional resources to better interpret the generated transcriptional findings. Our findings identify robust acute kidney injury (AKI-induced) developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species. These results would expand the current understanding of the pathophysiology of AKI and potentially offer novel targets for additional studies to enhance the translational transition of AKI research.NEW & NOTEWORTHY Our findings identify robust acute kidney injury (AKI)-induced developmental reprogramming of macrophages (MΦ) with the expansion of C1Q+, CD163+ MΦ that is independent of the etiology of AKI and conserved across mouse and human species.

Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin ß1.

BACKGROUND: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.

Toxic Nephropathies of the Tubulointerstitium: Core Curriculum 2024.

Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney's primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.

IgG4-related kidney disease: Clinicopathologic features, differential diagnosis, and mimics.

IgG4-related kidney disease (IgG4-RKD) encompasses all forms of kidney disease that are part of IgG4-related disease (IgG4-RD). First recognized as IgG4-related tubulointerstitial nephritis (IgG4-TIN), and then IgG4-related membranous glomerulonephritis (IgG4-MGN), we now recognize additional patterns of interstitial nephritis, glomerular disease, and vascular disease that can be seen as part of IgG4-RKD. The clinical presentation is variable and can include acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction. While usually associated with other organ involvement by IgG4-RD, kidney-alone involvement is present in approximately 20 % of IgG4-RKD. Compared to IgG4-RD overall, patients with IgG4-RKD are more likely to show increased serum IgG4 or IgG, and more likely to have hypocomplementemia. In this review, we extensively cover other types of autoimmune and plasma cell-rich interstitial nephritis, mass forming inflammatory diseases of the kidney, and other mimics of IgG4-TIN, in particular ANCA-associated disease.

Rare renal proximal tubular dysfunctions in primary biliary cholangitis.

INTRODUCTION: Renal involvement of primary biliary cholangitis (PBC) usually presents as distal renal tubular acidosis. Proximal tubular (PT) dysfunctions in PBC were rarely reported with unclear clinicopathological characteristics and renal prognosis. METHODS: We identified 11 cases of PBC with PT dysfunctions (PBC-PT). Their medical document, kidney pathology, and follow-up data were retrospectively reviewed and analyzed. RESULTS: The 11 PBC-PT patients were mainly middle-aged (57.8 ± 5.2 years) females (81.8%). Most of them were asymptomatic PBC (7, 63.6%) with a high prevalence of elevated serum immunoglobulin M (IgM, 81.8%) and G (IgG, 54.5%) levels. In the kidney, they had a mean estimated glomerular filtration rate (eGFR) level of 46.54 ± 23.03 ml/min/1.73m2, and 81.8% of them had eGFR below 60 ml/min/1.73m2. They showed different degrees of PT dysfunctions, including hyperuricosuria, hypouricemia, normoglycemic glycosuria, generalized aminoaciduria, hyperphosphaturia, and hypophosphatemia. Their kidney pathology showed tubulointerstitial nephritis with lymphoplasmacytic infiltrates, brush border defects, and proximal tubulitis. After glucocorticoids treatment, the PT dysfunctions manifesting as hypophosphatemia, hypouricemia, and renal glycosuria all recovered, and the eGFR levels were improved from 43.24 ± 19.60 ml/min/1.73m2 to 55.02 ± 21.14 ml/min/1.73m2 (p = 0.028), accompanied by significant improvements of serum IgM levels (from 5.97 ± 4.55 g/L to 2.09 ± 1.48 g/L, p = 0.019). CONCLUSIONS: The PT dysfunctions were rare in PBC patients, and glucocorticoids treatment could benefit the improvements of eGFR and tubular functions.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).

A case of acute kidney injury due to native kidney BK polyomavirus-associated nephropathy in a human T-lymphotropic virus type 1 carrier.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) has become a major cause of kidney dysfunction and graft loss in kidney transplant recipients. On rare occasion, polyomavirus has also been known to affect native kidneys of immunocompromised individuals. Only a small number of opportunistic infections have been reported in the carrier phase of human T-lymphotropic virus type 1 (HTLV-1). This is the first reported case of BKPyVAN in native kidneys of an HTLV-1 carrier. CASE PRESENTATION: A 61-year-old man was referred to our hospital from a primary care physician for work-up and treatment of pneumonia. He was diagnosed with Pneumocystis pneumonia and identified as a HTLV-1 carrier who had not yet developed adult T-cell leukemia (ATL). The pneumonia was successfully treated with sulfamethoxazole-trimethoprim. He had never been diagnosed with any kind of kidney dysfunction. Laboratory investigations showed a serum creatinine of 5.3 mg/dL, and urinary sediment showed cells with nuclear enlargement and inclusion bodies suggesting viral infection. The urinary Papanicolaou stain showed inclusions in swollen, ground-glass nuclei, typical of "decoy cells". Renal biopsy showed degeneration of tubules with epithelial enlargement, vacuolar degeneration, nuclear inclusion bodies, and detachment from the tubular basement membrane. Tubular nuclei showed positive staining positive for simian virus 40 large-T antigen. Polymerase chain reaction tests for BK polyomavirus DNA of both urine and plasma were positive. These findings confirmed a diagnosis of BKPyVAN. Intravenous immunoglobulin therapy did not improve renal function, necessitating maintenance hemodialysis therapy. CONCLUSIONS: BKPyVAN should be considered when acute kidney injury occurs with opportunistic infection. HTLV-1 carriers can develop opportunistic infections even before the onset of ATL.

[Clozapine-induced Tubulointerstitial Nephritis].

Tubulointerstitial nephritis is a common cause of acute renal failure, in two thirds of cases it is associated with drugs (mostly antimicrobials and NSAIDs), in 5-10% of cases it is associated with infections (bacterial/viral/parasitic), in 5-10% of cases it is idiopathic (this is the case of the TINU syndrome characterized by interstitial nephritis and bilateral uveitis, and the anti-glomerular basal membrane antibody syndrome), and finally in 10% of cases it is associated with systemic diseases (sarcoidosis, by Sjogren, LES). The pathogenesis is based on a cell-mediated immune response and in most cases removing the causative agent is the gold standard of therapy. However, a percentage of patients, in a variable range from 30% to 70% of cases, do not fully recover renal function, due to the rapid transformation of the interstitial cell infiltrate into vast areas of fibrosis. Clozapine is a second generation atypical antipsycothic usually used for the treatment of schizophrenia resistant to other types of treatment; it can cause severe adverse effects among which the best known is a severe and potentially fatal neutropenia, furthermore a series of uncommon adverse events are recognized including hepatitis, pancreatitis, vasculitis. Cases of acute interstitial tubular nephritis associated with the use of clozapine have been described in the literature, although this complication is rare. Medical personnel using this drug need to be aware of this potential and serious side effect. We describe the case of a 48-year-old man who developed acute renal failure after initiation of clozapine.

Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities.

CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats. Wistar rats were divided in 3 groups. Group 1 (n = 6) had free access to drinking water (control group). Group 2 (n = 8) was water deprived for 10 h per 24 h, 5 days/week and placed in an incubator (37 °C) for 30 min/h during water deprivation. Group 3 (n = 8) underwent daily oral gavage with cyclosporine (40 mg/kg body weight). After 28 days, renal function, histopathology and proteomic signatures were analysed. Cyclosporine-treated rats developed focal regions of atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining revealed enlarged argyrophilic granules in affected proximal tubules, identified as lysosomes by immunofluorescent staining. Electron microscopy confirmed the enlarged and dysmorphic phenotype of the lysosomes. Overall, these kidney lesions resemble those that have been previously documented in farmers with CINAC. Dehydration resulted in none of the above histopathological features. Proteomic analysis revealed that dehydration and cyclosporine both induce injury pathways, yet of a clear distinct nature with a signature of toxicity only for the cyclosporine group. In conclusion, both cyclosporine and dehydration are injurious to the kidney. However, dehydration alone does not result in kidney histopathology as observed in CINAC patients, whereas cyclosporine administration does. The histopathological analogy between CINAC and calcineurin inhibitor nephrotoxicity in rats and humans supports the involvement of an as-yet-unidentified environmental toxin in CINAC etiology.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants-5-Years Follow-Up.

BACKGROUND: Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. PURPOSE: The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. MATERIAL AND METHODS: Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. RESULTS: Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08). CONCLUSIONS: Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Renal sarcoidosis presenting with chronic kidney disease and hypercalcemia.

Sarcoidosis is a multisystem inflammatory disease that most frequently affects the lungs, lymph nodes, eyes, and skin. Renal involvement is clinically rare. We describe a 72-year-old male who presented with chronic kidney disease and elevated serum calcium and angiotensin-converting enzyme. Renal biopsy pathology showed chronic granulomatous interstitial nephritis. Renal function was significantly improved after glucocorticoid therapy. This case emphasizes that chronic kidney disease and hypercalcemia can be clues for renal sarcoidosis. Early renal biopsy and projective treatment is beneficial for renal outcome.

Native BK Polyomavirus Nephropathy in an Orthotopic Heart Transplant Patient.

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive nephrolithiasis requiring ureteral stenting. Kidney biopsy demonstrated evidence of polyomavirus nephritis. Serum BK viral load was elevated. Despite reducing immunosuppression and initiating leflunomide, viral clearance was never achieved. The patient experienced progressive failure to thrive before ultimately transitioning to hospice care and dying. The intensity of immunosuppression is a well-known risk factor for viral replication; ureteral stenting has also been associated with BKVN. However, since clinical manifestations of BK viral infections often include a genitourinary (GU) tract pathology, it is important for clinicians to consider BKVN in patients with NRSOT with progressive renal dysfunction, especially in the clinical context of known GU disease.

Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes of acute kidney injury with diagnosis-specific treatment options. However, due to the need to obtain a kidney biopsy for histological confirmation, AIN diagnosis can be delayed, missed, or incorrectly assumed. Here, we identify and validate urinary CXCL9, an IFN-γ-induced chemokine involved in lymphocyte chemotaxis, as a diagnostic biomarker for AIN.MethodsIn a prospectively enrolled cohort with pathologist-adjudicated histological diagnoses, termed the discovery cohort, we tested the association of 180 immune proteins measured by an aptamer-based assay with AIN and validated the top protein, CXCL9, using sandwich immunoassay. We externally validated these findings in 2 cohorts with biopsy-confirmed diagnoses, termed the validation cohorts, and examined mRNA expression differences in kidney tissue from patients with AIN and individuals in the control group.ResultsIn aptamer-based assay, urinary CXCL9 was 7.6-fold higher in patients with AIN than in individuals in the control group (P = 1.23 × 10-5). Urinary CXCL9 measured by sandwich immunoassay was associated with AIN in the discovery cohort (n = 204; 15% AIN) independently of currently available clinical tests for AIN (adjusted odds ratio for highest versus lowest quartile: 6.0 [1.8-20]). Similar findings were noted in external validation cohorts, where CXCL9 had an AUC of 0.94 (0.86-1.00) for AIN diagnosis. CXCL9 mRNA expression was 3.9-fold higher in kidney tissue from patients with AIN (n = 19) compared with individuals in the control group (n = 52; P = 5.8 × 10-6).ConclusionWe identified CXCL9 as a diagnostic biomarker for AIN using aptamer-based urine proteomics, confirmed this association using sandwich immunoassays in discovery and external validation cohorts, and observed higher expression of this protein in kidney biopsies from patients with AIN.FundingThis study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awards K23DK117065 (DGM), K08DK113281 (KM), R01DK128087 (DGM), R01DK126815 (DGM and LGC), R01DK126477 (KNC), UH3DK114866 (CRP, DGM, and FPW), R01DK130839 (MES), and P30DK079310 (the Yale O'Brien Center). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Clinical and Prognostic Factors in Patients with IgG4-Related Kidney Disease.

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.

Karyomegalic interstitial nephritis as a rare cause of kidney graft dysfunction: case report and review of literature.

Karyomegalic interstitial nephritis (KIN) is a rare cause of chronic interstitial nephritis characterized by enlarged renal tubular epithelial nuclei. The first case of KIN reported in a kidney graft was in 2019. Here, we report the first case of KIN in 2 brothers receiving kidneys from 2 different unrelated living donors. A male kidney transplant recipient with focal segmental glomerulosclerosis as the original kidney disease presented with graft impairment and proteinuria, and graft biopsy revealed KIN. This patient had a brother who was also a kidney transplant recipient and had one episode of graft impairment and was diagnosed with KIN as well.

Favorable course of leptospirosis and hantavirus-induced acute tubulointerstitial nephritis under corticosteroid treatment.

BACKGROUND: We present two children with acute tubulointerstitial nephritis (ATIN) caused by leptospirosis in a 12-year-old boy and hantavirus in a 10-year-old girl. The role of glucocorticoids in the management of ATIN triggered by infectious agents is unclear. CASE-DIAGNOSIS/TREATMENT: Both children were hospitalized with jaundice, elevated serum creatinine, and thrombocytopenia. There was no oliguria or hypertension. Urine analysis revealed tubular proteinuria. Kidney biopsy was performed on one patient and showed tubulointerstitial inflammation with mild mesangial proliferation. Both patients were treated with glucocorticoids in view of deteriorating kidney function with respective serum creatinine values of 5.2 and 4.1 mg/dl. Both children exhibited an excellent clinical and biochemical response to treatment. Neither of the patients required dialysis. Positive serology test results indicated a recent leptospirosis and hantavirus infection. CONCLUSIONS: Leptospirosis and hantavirus associated ATIN share common clinical and biochemical features. Due to the low incidence in Europe these infectious causes of kidney dysfunction may be overlooked. Glucocorticoids may be considered in the management of ATIN.

The Overlap of Kidney Failure in Extrapulmonary Sarcoidosis in Children-Case Report and Review of Literature.

Sarcoidosis is a non-necrotizing granulomatous inflammatory multisystemic disorder of unknown etiology. In children, as in adults, it can involve a few or all organ systems to a varying extent and degree, entailing multisystemic manifestations. Kidney involvement in pediatric-onset adult-type sarcoidosis is rare, with a wide range of renal manifestations, most of them related to calcium metabolism. Children with renal sarcoidosis tend to be more symptomatic than adults, although male patients have a higher prevalence. We present the case of a 10-year-old boy who presented with advanced renal failure with nephrocalcinosis and important hepatosplenomegaly. The diagnosis was established by histopathological examination, with consequent cortisone therapy and hemodialysis. This review emphasizes that sarcoidosis should be considered in the differential diagnosis of pediatric patients with acute kidney insufficiency or chronic kidney disease of an unknown etiology. As far as we know, this is the first study regarding extrapulmonary sarcoidosis in children from Romania.

The Spectrum of Biopsy-Proven Kidney Diseases, Causes, and Renal Outcomes in Acute Kidney Injury Patients.

INTRODUCTION: Acute kidney injury (AKI) is a group of highly heterogeneous, complicated clinical syndromes. Although kidney biopsy plays an irreplaceable role in evaluating complex AKI, a few studies have focused on the clinicopathology of AKI biopsies. This study analyzed the pathological disease spectrum, causes, and renal outcomes of biopsied AKI patients. METHODS: We retrospectively included 2,027 AKI patients who underwent kidney biopsies at a national clinical research center of kidney diseases from 2013 through 2018. To compare the biopsied AKI cases without and with coexisting glomerulopathy, patients were classified into acute tubular/tubulointerstitial nephropathy-associated AKI (ATIN-AKI) and glomerular disease-associated AKI (GD-AKI) groups. RESULTS: Of 2,027 biopsied AKI patients, 65.1% were male, with a median age of 43 years. A total of 1,590 (78.4%) patients had coexisting GD, while only 437 (21.6%) patients had ATIN alone. The AKI patients with GD mainly (53.5%) manifested as stage 1 AKI, while most ATIN-AKI patients (74.8%) had stage 3 AKI. In the ATIN-AKI group, 256 (58.6%) patients had acute interstitial nephritis (AIN), and 77 (17.6%) had acute tubular injury (ATI). ATIN-AKI was mainly caused by drugs in 85.5% of AIN and 63.6% of ATI cases, respectively. In AKI patients with coexisting GD, the leading pathological diagnoses in over 80% of patients were IgA nephropathy (IgAN, 22.5%), minimal change disease (MCD, 17.5%), focal segmental glomerulosclerosis (FSGS, 15.3%), lupus nephritis (LN, 11.9%), membranous nephropathy (MN, 10.2%), and ANCA-associated vasculitis (AAV, 4.7%). A total of 775 patients were followed up within 3 months after renal biopsy; ATIN-AKI patients achieved statistically higher complete renal recovery than the GD-AKI patients (83.5% vs. 70.5%, p < 0.001). CONCLUSIONS: Most biopsied AKI patients have coexisting GD, while ATIN alone is seen less frequently. ATIN-AKI is mainly caused by drugs. In GD-AKI patients, IgAN, MCD, FSGS, LN, MN, and AAV are the leading diagnoses. Compared to AKI patients without GD, patients with GD suffer from worse renal function recovery.