Global burden of anticancer drug-induced acute kidney injury and tubulointerstitial nephritis from 1967 to 2023.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

Association between inflammatory bowel disease, nephrolithiasis, tubulointerstitial nephritis, and chronic kidney disease: A propensity score-matched analysis of US nationwide inpatient sample 2016-2018.

OBJECTIVES: The incidence and prevalence of inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), are increasing globally. We aimed to evaluate the potential association between IBD and nephrolithiasis, tubulointerstitial nephritis, and chronic kidney disease (CKD). METHODS: Data of hospitalized adults ≥20 years of age were extracted from the U.S. National Inpatient Sample (NIS) during 2016-2018. Patients with UC, CD, or CKD were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Propensity score matching (PSM) analysis (1:1) was conducted to balance the characteristics between groups. Logistic regression analyses were performed to determine the relationships between UC or CD and kidney conditions. RESULTS: Three cohorts were included for analysis after PSM analysis. Cohorts 1, 2 and 3 contained 235 262 subjects (117 631 with CD or without IBD), 140 856 subjects (70 428 with UC or without IBD), and 139 098 subjects (69 549 with CD or UC), respectively. Multivariate analysis revealed that compared to non-IBD individuals, CD patients were significantly associated with greater odds for nephrolithiasis (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 2.08-2.43), tubulointerstitial nephritis (aOR 1.31, 95% CI 1.24-1.38), CKD at any stage (aOR 1.28, 95% CI 1.24-1.32), and moderate-to-severe CKD (aOR 1.22, 95% CI 1.17-1.26), while UC was associated with a higher rate of nephrolithiasis. Compared to UC, CD was associated with higher odds for all such kidney conditions. CONCLUSIONS: Patients with CD are more likely to have nephrolithiasis, tubulointerstitial nephritis, CKD at any stage, and moderate-to-severe CKD compared to non-IBD individuals.

Tubulointerstitial nephritis and uveitis in children during the COVID-19 pandemic: report of four cases.

Tubulointerstitial nephritis and uveitis (TINU) is a rare autoimmune disorder often triggered by drugs and infections. Since the onset of the COVID-19 pandemic, we have observed an unusual cluster of paediatric cases. Four children (3 females) were diagnosed with TINU (median age 13 years) following a kidney biopsy and ophthalmologic assessment. Presenting symptoms included abdominal pain (3 cases), fatigue, weight loss and vomiting (2 cases). At presentation, median eGFR was 50.3 ml/min/1.73m2 (range 19.2-69.3). Anaemia was common (3 cases) with median haemoglobin of 10.45 g/dL (range 8.4-12.1). Two patients were hypokalaemic and 3 had non-hyperglycaemic glycosuria. Median urine protein:creatinine ratio was 117 mg/mmol (range 68-167). SARS-CoV-2 antibodies were detected in 3 cases at presentation. All were asymptomatic for COVID-19 with a negative PCR. Kidney function improved following high-dose steroids. However, disease relapse was observed during steroid tapering (2 cases) and upon discontinuation (2 cases). All patients responded well to further high dose steroids. Mycophenolate mofetil was introduced as a steroid-sparing agent. At latest follow up (range 11-16 months), median eGFR was 109.8 ml/min/1.73m2. All four patients continue on mycophenolate mofetil, with 2 patients applying topical steroids for uveitis. Our data suggest that SARS-CoV-2 infection might be a trigger for TINU.

Efficacy and safety of methylprednisolone pulse followed by oral prednisone vs. oral prednisone alone in sarcoidosis tubulointerstitial nephritis: a randomized, open-label, controlled clinical trial.

BACKGROUND: We determine the benefit of pulsed methylprednisolone for improving kidney function in patients with sarcoidosis tubulointerstitial nephritis. METHODS: We conducted a multicenter, prospective, randomized, open-label, controlled trial in patients with biopsy-proven acute tubulointerstitial nephritis caused by sarcoidosis at 21 sites in France. Patients were randomly assigned to receive a methylprednisolone pulse 15 mg/kg/day for 3 days, then oral prednisone (MP group) or oral prednisone 1 mg/kg/day alone (PRD group). The primary end point was a positive response at 3 months, defined as a doubling of estimated glomerular filtration rate (eGFR) compared with the eGFR before randomization. RESULTS: We randomized 40 participants. Baseline eGFR before PRD was 22 mL/min/1.73m2 {interquartile range [IQR], 16-44} and before MP was 25 mL/min/1.73m2 (IQR, 22-36) (P = .3). The two groups did not differ in underlying pathological lesions, including mean percentage of interstitial fibrosis and intensity of interstitial infiltrate. In the intent-to-treat population, the median eGFR at 3 months did not significantly differ between the PRD and MP groups: 45 (IQR, 34-74) and 46 (IQR, 39-65) mL/min/1.73m2. The primary end point at 3 months was achieved in 16 of 20 (80%) PRD patients and 10 of 20 (50%) MP patients (P = .0467). The eGFR was similar between the two groups after 1, 3, 6, and 12 months of treatment. For both groups, eGFR at 1 month was strongly correlated with eGFR at 12 months (P < .0001). The two groups did not differ in severe adverse events. CONCLUSION: Compared with a standard oral steroid regimen, intravenous MP may have no supplemental benefit for renal function in patients with tubulointerstitial nephritis caused by sarcoidosis.Trial Registration: ClinicalTrials.gov: NCT01652417; EudraCT: 2012-000149-11.

Prevalence of hereditary tubulointerstitial kidney diseases in the German Chronic Kidney Disease study.

Hereditary chronic kidney disease (CKD) appears to be more frequent than the clinical perception. Exome sequencing (ES) studies in CKD cohorts could identify pathogenic variants in ~10% of individuals. Tubulointerstitial kidney diseases, showing no typical clinical/histologic finding but tubulointerstitial fibrosis, are particularly difficult to diagnose. We used a targeted panel (29 genes) and MUC1-SNaPshot to sequence 271 DNAs, selected in defined disease entities and age cutoffs from 5217 individuals in the German Chronic Kidney Disease cohort. We identified 33 pathogenic variants. Of these 27 (81.8%) were in COL4A3/4/5, the largest group being 15 COL4A5 variants with nine unrelated individuals carrying c.1871G>A, p.(Gly624Asp). We found three cysteine variants in UMOD, a novel missense and a novel splice variant in HNF1B and the homoplastic MTTF variant m.616T>C. Copy-number analysis identified a heterozygous COL4A5 deletion, and a HNF1B duplication/deletion, respectively. Overall, pathogenic variants were present in 12.5% (34/271) and variants of unknown significance in 9.6% (26/271) of selected individuals. Bioinformatic predictions paired with gold standard diagnostics for MUC1 (SNaPshot) could not identify the typical cytosine duplication ("c.428dupC") in any individual, implying that ADTKD-MUC1 is rare. Our study shows that >10% of selected individuals carry disease-causing variants in genes partly associated with tubulointerstitial kidney diseases. COL4A3/4/5 genes constitute the largest fraction, implying they are regularly overlooked using clinical Alport syndrome criteria and displaying the existence of phenocopies. We identified variants easily missed by some ES pipelines. The clinical filtering criteria applied enriched for an underlying genetic disorder.

Manifestations of renal involvement in sarcoidosis - case series.

Renal involvement is observed in 30% of sarcoidosis cases, but the exact occurrence is unknown, and the current numbers are estimated to be underestimated. The most common manifestation of renal sarcoidosis is interstitial nephritis, but other presentations are also possible, with specific histopathological and laboratory findings. Glomerulopathies, nephrocalcinosis and nephrolithiasis are among the most commonly seen types of renal involvement. CASE REPORTS: We would like to show a case series describing four patients with varying renal manifestations of sarcoidosis: membranous nephropathy, granulomatous interstitial nephritis, IgA nephropathy and chronic kidney disease. The diagnosis of sarcoidosis can precede, present simultaneously with or follow the onset of renal manifestations. Our patients also showcase varying clinical pictures of renal sarcoidosis with different changes in renal parameters. CONCLUSIONS: The involvement of kidneys in sarcoidosis is multifaceted and may pose a diagnostic difficulty, and a diagnostic kidney biopsy is often needed. Chronic sarcoidosis patients should undergo regular screening for renal involvement to introduce proper management quickly and effectively.

Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data.

BACKGROUND: Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record. METHODS: In patients who underwent a kidney biopsy at Yale University between 2013 and 2018, we tested the association of >150 variables with AIN, including demographics, comorbidities, vital signs and laboratory tests (training set 70%). We used least absolute shrinkage and selection operator methodology to select prebiopsy features associated with AIN. We performed area under the receiver operating characteristics curve (AUC) analysis with internal (held-out test set 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested the change in model performance after the addition of urine biomarkers in the Yale AIN study. RESULTS: We included 393 patients (AIN 22%) in the training set, 158 patients (AIN 27%) in the test set, 1118 patients (AIN 11%) in the validation set and 265 patients (AIN 11%) in the Yale AIN study. Variables in the selected model included serum creatinine {adjusted odds ratio [aOR] 2.31 [95% confidence interval (CI) 1.42-3.76]}, blood urea nitrogen:creatinine ratio [aOR 0.40 (95% CI 0.20-0.78)] and urine dipstick specific gravity [aOR 0.95 (95% CI 0.91-0.99)] and protein [aOR 0.39 (95% CI 0.23-0.68)]. This model showed an AUC of 0.73 (95% CI 0.64-0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74 (95% CI 0.69-0.79)]. The AUC improved to 0.84 (95% CI 0.76-0.91) upon the addition of urine interleukin-9 and tumor necrosis factor-α. CONCLUSIONS: We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon the addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.

Tubulointerstitial nephritis and uveitis in Northern Ireland.

OBJECTIVES: This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented. METHODS: Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis. RESULTS: The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment. CONCLUSIONS: TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.

Characteristics of renal sarcoidosis and tubulointerstitial nephritis and uveitis syndrome in Slovenia: An analysis of the national renal biopsy registry and patient datasets in the last decade.

BACKGROUND: Sarcoidosis is characterized by granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous tubulointerstitial nephritis (TIN) is the predominant histologic feature. TIN is also a hallmark of tubulointerstitial nephritis and uveitis (TINU) syndrome. Diagnoses of both sarcoidosis and TINU syndrome are usually made by exclusion and by combining clinical and histological findings, and often remain misdiagnosed. The aim of this retrospective study was to determine the characteristics of renal sarcoidosis and TINU syndrome in Slovenia in the last decade (2010 - 2020). MATERIALS AND METHODS: A thorough search of the national database of renal biopsies from January 2010 to December 2020 was performed. Inclusion criteria were TIN and a clinical history of either sarcoidosis or TINU syndrome. To compare the characteristics of our cohort with others, we also reviewed the global literature reported since 2010. RESULTS: 13 patients (9 female, 4 male) were included in our study. Indications for kidney biopsy were acute kidney injury (n = 8), acute exacerbation of chronic kidney disease (n = 4), and proteinuria (n = 1). Seven patients had clinical and histological evidence of sarcoidosis, and 6 patients were classified as having TINU syndrome. All patients were treated with corticosteroids. Of the 13 patients, 11 had improved kidney function 6 months after treatment, and proteinuria decreased in 9 patients. One patient was on dialysis at the time of diagnosis and remained so thereafter. CONCLUSION: Renal sarcoidosis and TINU syndrome are rare but important causes of kidney injury, with a favorable long-term prognosis if properly diagnosed and treated in a timely manner.

Long-term outcome of biopsy-proven idiopathic tubulointersitial nephritis with or without uveitis in children-a nationwide follow-up study.

BACKGROUND: Only a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU. METHODS: All patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively. RESULTS: Fifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8-16.9) years and median follow-up time was 5.7 (1.1-21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 µmol/l (47-1,016) and that of eGFR 47 ml/min/1.73m2 (8-124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2 (median 83; 61-89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted. CONCLUSIONS: Our study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted. A higher resolution version of the Graphical abstract is available as Supplementary information.

[Etiologies and prognostic factors of acute interstitial nephritis]. / Étiologies et facteurs pronostiques des néphropathies interstitielles aiguës.

INTRODUCTION: Acute interstitial nephritis represents a clinically and etiologically heterogeneous group of kidney diseases. The aim of our study was to explore the main causes of biopsy-proven acute interstitial nephritis and to identify predictive factors of renal outcome. METHODS: We conducted a retrospective monocentric study which included patients with biopsy proven AIN, followed in our department during the period between 1980 and 2018. The non-recovery of kidney function or an estimated glomerular filtration rate˂60 mL/min/1.73 m2 were considered as a worse renal outcome. RESULTS: A total of 65 acute interstitial nephritis patients were enrolled. The mean age of patients was 41.3±16 years with a female predominance (78%). Drug-induced etiology was the most common (29%). The most frequent culprit drugs in our study were NSAID followed by antibiotics. The renal prognosis was unfavorable in 21 cases (32%). The independent predictive factors for renal outcome were : a percentage of sclerotic glomeruli greater than 15% (P=0.004), absence of interstitial edema (P˂0.001), non-use to corticosteroid therapy (P=0.02) and a delay in initiating corticosteroid therapy greater than 21 days (P=0.02). CONCLUSION: Drugs currently represent the most common cause of acute interstitial nephritis. The renal prognosis is often favorable, but the progression can be towards chronic renal failure in the event of diagnostic and therapeutic delay. Our data suggest a beneficial influence of steroids on the outcome of acute interstitial nephritis.

Frequency and etiology of tubulo-interstitial nephritis in an adult renal biopsies in a tertiary renal care hospital: A single-center study.

Tubulo-interstitial nephritis (TIN) is an important cause of acute renal failure which may progresses to chronic kidney disease (CKD). TIN is often under diagnosed with there are no specific signs and symptoms. As this entity has paramount importance, so we evaluated the frequency and etiological of TIN both acute TIN (ATIN) and chronic tububulo-interstitial nephritis (CTIN) in renal biopsies. This is a retrospective observational, descriptive study carried out in the Department of Nephrology at The Kidney Centre Post Graduate Training Institute from 2004 to 2016. A total of 1560 adult renal biopsies were done during this period with 125 biopsies of TIN, of which 70 (56%) cases were ATIN and 55 (44%), were CTIN. Thirty-eight (30%) patients had a history of taking proton-pump inhibitors, use of various antibiotics in 21 (16%) cases, and 11 (8%) patients had a history of taking Hakeemi (traditional healer using herbs and sometimes trace amounts of heavy metals) medications. The incidence of TIN is higher than suspected and can be caused by variety of etiological agents. Therefore, clinical awareness will help in the diagnosis and early identification of the disease.

Glomerulonephritis Histopathological Pattern Change.

BACKGROUND: Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and can lead to chronic kidney disease (CKD) and end stage kidney disease (ESKD). Kidney biopsy is the diagnostic procedure of choice with variable indications from center to center. It helps in identifying the exact specific diagnosis, assessing the level of disease activity and severity, and hence aids in proper therapy and helps predicting prognosis. There is a global change of pattern of glomerular disease over the last five decades. METHODS: Retrospective analysis of all kidney biopsies (545 cases) that were done in patients over 12 year-old over last six years in four major hospitals in Kuwait. The indications for kidney biopsy were categorized into six clinical syndromes: nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome plus acute kidney injury (AKI), sub-nephrotic proteinuria plus AKI, isolated hematuria, and Unexplained renal impairment. We calculated the incidence of each type of kidney disease and indication of biopsy. RESULTS: most common indication of kidney biopsy was sub-nephrotic proteinuria associated with AKI in 179 cases (32.8%). Primary Glomerulonephritis was the main diagnosis that was reported in 356 cases (65.3%). Immunoglobulin A Nephropathy (IgAN) was the commonest lesion in primary glomerulonephritis in 85 (23.9%) cases. Secondary Glomerulonephritis was diagnosed in 134 cases (24.6%), 56 (41.8%) of them were reported as lupus nephritis cases. In young adults (below 18 years of age) there were 31 cases reviews, 35.5% were found to have minimal change disease (MCD). CONCLUSION: IgAN is the commonest glomerulonephritis in primary nephrotic syndromes in Kuwait over the past six years. Lupus nephritis is the leading secondary glomerulonephritis diagnosis.

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.

Cistus salviifolius Toxicity in Cattle.

Toxicity related to consumption of Cistus sp. pl. has been described in ruminants in some countries. This report describes the clinical and pathological findings of Cistus salviifolius toxicosis in 3 beef cattle herds located in 2 different areas of Sicily, Italy. Outbreaks were observed after grazing in poor winter pasture where C. salviifolius was abundant. Mean morbidity and mortality were 29% and 21%, respectively. Most of the affected animals (6 to 36 months old) showed anorexia, weight loss, and pollakiuria culminating in recumbency and death. Occasionally, abortion and neurological signs were observed. In animals with acute signs, there was a moderate decrease of sodium and chloride concentrations in serum. Animals with chronic signs showed an increase of serum urea, creatine phosphokinase (CPK), aspartate transaminase (AST), lactate dehydrogenase (LDH), and phosphorus and a decrease in total serum protein, calcium, chloride, and magnesium concentrations. Moderate anemia and slight neutropenia, lymphocytosis, and eosinophilia were detected in all groups. At necropsy, the main lesion was severe distention of the urinary bladder with turbid hemorrhagic urine and crystalluria. Histologically, chronic cystitis, interstitial nephritis, eosinophilic enteritis, and nonsuppurative necrotizing hepatitis were observed. To our knowledge, this is the first report of C. salviifolius toxicosis in cattle in Italy.

Epidemiologic data of biopsy-proven renal diseases: Experience from a single center in South India.

An analysis of the renal biopsy data is important to understand the regional prevalence of various biopsy-proven renal diseases (BPRDs). We analyzed our renal biopsy registry over a period of 15 years. We retrospectively reviewed all the renal biopsies performed at Arun Kidney Centre, Vijayawada, Andhra Pradesh, from January 2004 to March 2018. All biopsies were analyzed using immunofluorescence and light microscopy. A total of 924 renal biopsies were considered for the analysis. The mean age of the patients was 32 ± 14.77 years, with a male:female ratio of 1.5:1. Nephrotic syndrome (46.1%) was the most common indication for renal biopsy, followed by rapidly progressive renal failure (11%) and rapidly progressive glomerulonephritis (9.9%). Primary glomerulonephritis (PGN) was the most common entity (66.8%), followed by tubulointerstitial disease (17.5%), secondary glomerulonephritis (SGN) (12.1%), and vascular nephropathies (3.5%). Among cases with PGN, the most common causes were minimal change disease (22.98%), immunoglobulin A nephropathy (21.3%), and membranous nephropathy (17%), whereas the most common SGN was lupus nephritis (60.7%). Acute tubulointerstitial nephritis (61.1%) was the most common tubulointerstitial disease, whereas antineutrophil cytoplasmic antibody vasculitis (56.3%) was the most common vascular nephropathy. We also noticed significant changing trends in many nephropathies. Our study provides epidemiologic data regarding the various BPRDs and also the changing trends of the individual renal diseases.

High-Risk Indicators of Renal Involvement in Primary Sjogren's Syndrome: A Clinical Study of 1002 Cases.

OBJECTIVE: A retrospective analysis of clinical characteristics and immunological manifestations of primary Sjogren's syndrome (pSS) patients with or without renal involvement was conducted in order to elucidate the potential risk factors of renal damage in pSS and evaluate the condition. METHODS: A total of 1002 patients, who fulfilled the 2002 classification criteria for pSS from the Second Affiliated Hospital of Shanxi Medical University, were enrolled in the cross-sectional study. Clinical, immunological, and histological characteristics were compared between pSS patients with and without renal involvement, and potential risk factors of renal involvements in pSS patients were examined by multivariate analysis. RESULTS: Among these pSS patients, there were 162 cases (16.17%) with and 840 cases (83.83%) without renal damage. Serious edema of both lower limbs, interstitial nephritis, and renal tubular acidosis were found in the pSS with renal damage group. Compared with simple pSS patients, the levels of creatinine, cystatin C, and alpha-1-microglobulin (α 1-MG) in the pSS with renal damage group were significantly increased. The difference between the two groups was statistically significant (P < 0.05). The AUC of the combination of creatinine and α 1-MG and creatinine, α 1-MG, and creatinine was statistically larger than that of creatinine, and the biomarker of the biggest AUC is the combination of creatinine and α 1-MG. CONCLUSION: The main clinical manifestations of pSS with renal damage were edema of the lower limbs, interstitial nephritis, and renal tubular acidosis. Creatinine and α 1-MG are effective indicators for renal function in pSS, which may provide a better understanding for clinical decision-making.

Steroid therapy in drug induced acute interstitial nephritis- Retrospective analysis of 83 cases.

Drug-induced acute interstitial nephritis (DIAIN) is a common cause of acute deterioration of renal function. Early diagnosis and discontinuation of the offending drug usually lead to recovery of renal function. Steroid administration further hastens the recovery. However, the outcome of steroid-treated DIAIN is not well studied in the Indian scenario. We aimed to study the clinical profile and one-year renal outcome of DIAIN patients treated with steroids. We performed a retrospective study in biopsy-proven acute interstitial nephritis (AIN) and presumptive DIAIN patients who did not respond to discontinuation of the offending drug after five days of the diagnosis of AIN. Eighty-three DIAIN patients were included who were treated with 500 mg of methylprednisolone for three consecutive days followed by prednisolone of 0.5-1 mg/kg tapered over four to six weeks. We evaluated clinical profile, serum creatinine (SCr), and need of renal replacement therapy at the end of one year. We divided the patients into two groups: 1st as complete responders group (CR) when SCr is <1.5 mg/dL at the end of one year and 2nd as incomplete responders (IR) when it is ≥1.5 mg/dL and evaluated the outcome between two groups. In total, there were 39 (47%) CR and 44 (53%) were IR. Diabetes mellitus, present in a significant number of cases 27 (33%) was associated with poor response to steroids. Most common offending agents recognized were antibiotics (34%), nonsteroidal anti-inflammatory drugs (25%), herbal medications (13%), proton pump inhibitors (10%), and miscellaneous drugs (18%). There was no correlation between drug category and response to steroids. Interstitial fibrosis in renal biopsy was associated with poor response to steroids (4 cases in CR and 35 cases in IR, P ≤0.0001). Neutrophilic predominance in biopsy was associated with favorable response to steroids. Initial SCr and initial the requirement of dialysis support was not helpful in predicting the response to steroids and final recovery.

Prospective Biopsy-Based Study of CKD of Unknown Etiology in Sri Lanka.

BACKGROUND AND OBJECTIVES: A kidney disease of unknown cause is common in Sri Lanka's lowland (dry) region. Detailed clinical characterizations of patients with biopsy-proven disease are limited, and there is no current consensus on criteria for a noninvasive diagnosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We designed a prospective study in a major Sri Lankan hospital servicing endemic areas to ascertain pathologic and clinical characteristics of and assess risk factors for primary tubulointerstitial kidney disease. We used logistic regression to determine whether common clinical characteristics could be used to predict the presence of primary tubulointerstitial kidney disease on kidney biopsy. RESULTS: From 600 new patients presenting to a tertiary nephrology clinic over the course of 1 year, 87 underwent kidney biopsy, and 43 (49%) had a biopsy diagnosis of primary tubulointerstitial kidney disease. On detailed biopsy review, 13 (30%) had evidence of moderate to severe active kidney disease, and six (15%) had evidence of moderate to severe chronic tubulointerstitial kidney disease. Patients with tubulointerstitial kidney disease were exclusively born in endemic provinces; 91% spent a majority of their lifespan there. They were more likely men and farmers (risk ratio, 2.0; 95% confidence interval, 1.2 to 2.9), and they were more likely to have used tobacco (risk ratio, 1.7; 95% confidence interval, 1.0 to 2.3) and well water (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). Three clinical characteristics-age, urine dipstick for protein, and serum albumin-could predict likelihood of tubulointerstitial kidney disease on biopsy (model sensitivity of 79% and specificity of 84%). Patients referred for kidney biopsy despite comorbid diabetes or hypertension did not experience lower odds of tubulointerstitial kidney disease. CONCLUSIONS: A primary tubulointerstitial kidney disease occurs commonly in specific regions of Sri Lanka with characteristic environmental and lifestyle exposures.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.