The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia: a prospective study in kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. METHODS: This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. RESULTS: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)). CONCLUSIONS: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.

Tubulointerstitial Nephritis and Uveitis Syndrome (TINU) after Intake of Dietary Supplement.

INTRODUCTION: The pathogenesis of tubulointerstitial nephritis with uveitis syndrome (TINU) is thought to be an interplay between environmental and genetic factors leading to an inappropriate immune response. METHODS: Report of a clinical case. RESULTS: We present a case of TINU syndrome which meets the clinical and anatomopathological features according to the classification criteria of the standardization of uveitis nomenclature (SUN) working group. The only possible causal agent was found to be the intake of a nutritional supplement. CONCLUSION: Our case highlights the role of environmental factors as triggers for this disorder.

Predictive Factors of BK Virus Development in Kidney Transplant Recipients and the Effect of Low-Dose Tacrolimus Plus Everolimus on Clinical Outcomes.

OBJECTIVES: This study aimed to determine the predictive factors of BK virus viremia/nephropathy in kidney transplant recipients and to evaluate the effects of low-dose tacrolimus plus everolimus. MATERIALS AND METHODS: This study included 3654 kidney transplant recipients. The patients were divided into 2 groups: group 1 were BK virus negative (n = 3525, 96.5%) and group 2 were BK virus positive (n = 129, viremia 3.5%, nephropathy 1%). Predictive factors were determined by receiver operating characteristic curve analysis and logistic regression models.We also divided and analyzed patients with BK virus viremia/nephropathy into 2 groups according to immunosuppressive changes. Group 2a had been switched to low-dose tacrolimus plus everolimus (n = 54, 41.9%), and group 2b had been switched to other immunosuppressive protocols (n = 75, 58.1%). RESULTS: We found that use of anti-T-cell lymphocyte globulin and tacrolimus, deceased donor transplant, and rejection were predictive factors for BK virus viremia/nephropathy. In addition, patients who had low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor regimens showed a low rate of BK virus development(only 6.2% of all cases). In Group 2a, both the BK polyomavirus-associated nephropathy rate (n = 23 [42.6%] vs n = 12 [16%] in group 2b; P = .001) and viral load (DNA > 104 copies/mL) (n = 49 [90.7%] vs n = 27 [36%] in group 2b; P = .001) were increased versus group 2b. Graft function, graft survival, viral clearance, and rejection rate were similar between the groups after protocol change. CONCLUSIONS: BK virus viremia/nephropathy rate was lower in patients who received low-dose calcineurin inhibitor plus mammalian target of rapamycin inhibitor protocols; the low-dose tacrolimus plus everolimus switch protocol after BK virus was more effective and safe than other protocols.

New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review.

The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN.

Acute Interstitial Nephritis with Glomerular Capillary IgA Deposition Following SARS-CoV-2 mRNA Vaccination.

We herein report a case of acute kidney injury (AKI) presenting as acute interstitial nephritis (AIN) after the first dose of the BNT162b2 mRNA vaccine against coronavirus disease 2019 (COVID-19). A 69-year-old man with a history of diabetes and hypertension presented with AKI 4 days after receiving the vaccine. Despite the administration of methylprednisolone pulse treatment, his renal function worsened, which prompted us to initiate temporal hemodialysis. His renal function subsequently improved, and a renal biopsy confirmed AIN and glomerular capillary IgA deposition without apparent crescents. The clinical history and histological findings suggest a relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and AIN as a rare side effect.

Interstitial Nephritis: Wherefrom, Wherein, and Whereto.

Abnormalities of the renal interstitium were noted early while identifying chronic kidney disease in 1827; however, interest in glomerular and vascular lesions was then distracted from their further study. As a complication of scarlet fever, interstitial lesions attracted attention in 1859 and came to be defined as acute interstitial nephritis in 1898. The chronic form of interstitial nephritis was traditionally attributed to pyelonephritis until the advent of kidney biopsy in the 1950s, when interstitial lesions were recognized as an independent primary cause of chronic kidney disease from studies of analgesic nephropathy and vesico-ureteral reflux. The term tubulointerstitial nephritis was introduced in 1963 and promoted to denote the role of the tubules in the pathogenesis and the clinical presentation of interstitial nephritis as tubular dysfunction. Studies since then have established that fibrotic tubulointerstitial nephritis lesions correlate best with the severity and progression of kidney diseases independent of their etiology.

Tubulointerstitial nephritis and uveitis syndrome and SARS-CoV-2 infection in an adolescent: just a coincidence in time?

BACKGROUND: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy. CASE-DIAGNOSIS/TREATMENT: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis. CONCLUSIONS: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness.

Characteristics, risk factors and outcome of BKV nephropathy in kidney transplant recipients: a case-control study.

BACKGROUND: Following kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR. METHODS: We conducted a retrospective case-control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan-Meier estimator. RESULTS: Sixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5-14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm3 and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01). CONCLUSIONS: BKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm3 and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis.

Renal disease in sarcoidosis patients in a German multicentric retrospective cohort study.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease potentially affecting every organ system. Renal involvement is reportedly rare, and the evidence consists of case reports and cohort studies. Systematic investigations are scarce and show a varying prevalence ranging from <1% to 30-50%. METHODS: We retrospectively analyzed data from patients with a recent diagnosis of sarcoidosis from five tertiary care centers focusing on renal sarcoidosis. RESULTS: We analyzed data from 327 patients with sarcoidosis between 2001 and 2021. Of 327 patients, 109 (33.3%) had probable or definite renal sarcoidosis. 90 (27.5%) had histopathologic confirmation. 57 (64%) had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The most prominent associated finding was an elevated soluble interleukin-2 receptor. Patients with renal sarcoidosis more frequently received glucocorticoids than other non-renal sarcoidosis patients (92% vs. 78%, p < 0.01). Also, azathioprine (38% vs. 16%, p < 0.001) and mycophenolate mofetil (5% vs. 1%, p < 0.05) were more frequently used in renal sarcoidosis compared to non-renal sarcoidosis, whereas methotrexate was used less frequently (7% vs. 17%, p < 0.05). CONCLUSIONS: Our data of the largest cohort with biopsy-confirmed renal sarcoidosis demonstrate a higher prevalence (27.5% of all patients) than previously published with a relevant disease burden. The urinary findings in most cases were only mildly abnormal, and some patients did not have renal biopsy despite abnormal urinary results. A renal workup should be performed in all patients with a new diagnosis of sarcoidosis.

Renal and Urological Disorders Associated With Inflammatory Bowel Disease.

Renal and urinary tract complications related to inflammatory bowel disease (IBD) have been relatively understudied in the literature compared with other extraintestinal manifestations. Presentation of these renal manifestations can be subtle, and their detection is complicated by a lack of clarity regarding the optimal screening and routine monitoring of renal function in IBD patients. Urolithiasis is the most common manifestation. Penetrating Crohn's disease involving the genitourinary system as an extraintestinal complication is rare but associated with considerable morbidity. Some biologic agents used to treat IBD have been implicated in progressive renal impairment, although differentiating between drug-related side effects and deteriorating kidney function due to extraintestinal manifestations can be challenging. The most common findings on renal biopsy of IBD patients with renal injury are tubulointerstitial nephritis and IgA nephropathy, the former also being associated with drug-induced nephrotoxicity related to IBD medication. Amyloidosis, albeit rare, must be diagnosed early to reduce the chance of progression to renal failure. In this review, we evaluate the key literature relating to renal and urological involvement in IBD and emphasize the high index of suspicion required for the prompt diagnosis and treatment of these manifestations and complications, considering the potential severity and implications of acute or chronic loss of renal function. We also provide suggestions for future research priorities.

Renal and urinary tract complications related to inflammatory bowel disease (IBD) are important but have been neglected in the literature. We emphasize the high index of suspicion required for the prompt diagnosis, treatment, and prevention of these manifestations and complications.

Hilar lymphadenopathy, development of tubulointerstitial nephritis, and dense deposit disease following Pfizer-BioNTech COVID-19 vaccination.

Despite the reports on glomerulonephritis associated with COVID-19 mRNA vaccines, no study has reported about the dense deposit disease (DDD). Here, we present a case of hilar lymphadenopathy after the COVID-19 mRNA vaccination, following which the patient developed tubulointerstitial nephritis (TIN) and DDD. A 74-year-old man received his second dose of mRNA vaccine, and on the next day, he developed fever, urticaria, and dyspnea. On further examination, he had pleural effusion and right hilar lymphadenopathies, which were improved with conservative therapy. After 48 days of the second vaccination, he developed renal dysfunction and new-onset hematuria. Light microscopy findings by renal biopsy revealed apparent mesangial cell proliferation, increased mesangial matrix in the glomeruli, and diffuse inflammatory cell infiltration in the interstitium. Immunofluorescence analysis revealed 1 + positive results for IgG and IgM, negative results for IgA, and 2 + positive results for C3 with a garland pattern on the capillary walls. Electron microscopy revealed that severe cell proliferation in the capillary rumen, and continuous, thickened, and highly dark-stained spotty dense deposits in the glomerular basement membrane; and noncontinuous spotty dense deposits in the tubular basement membrane. Based on the decrease in C3 and pathological findings, TIN accompanied with DDD was diagnosed. The mRNA vaccine might have contributed to the development of lymphadenopathies, TIN, and DDD in this case. Moreover, TIN and DDD might be associated with the activated alternative pathway induced by the mRNA vaccine.

Acute Interstitial Nephritis in the Pediatric Population: A Review of Etiologic Associations, Histologic Findings, and Clinical Outcome.

BACKGROUND: Acute interstitial nephritis (AIN) is an infrequent cause of acute kidney injury in the pediatric population with a broad range of etiologies. This retrospective review attempts to characterize AIN in the pediatric population, delineate etiologic factors, histologic features, and clinical outcome. MATERIALS AND METHODS: Institutional pathology reports were queried for a diagnosis of AIN between 1/2010 and 10/2021. Archived slides and reports and clinical records were reviewed. RESULTS: Twenty-four patients were identified whose ages ranged from 5 to 20 years. A 8 cases (37.5%) were characterized as tubulointerstitial nephritis and uveitis (TINU), 4 cases (16.7%) were associated with an autoimmune disease, 4 cases (16.7%) were likely drug induced, and 8 cases (37.5%) had unclear etiology. DISCUSSION: Although all cases of drug induced interstitial nephritis contained eosinophils they were not exclusive to drug induced interstitial nephritis. A prominent plasma cell infiltrate was seen in both cases of Sjögren's associated interstitial nephritis. The vast majority (n = 18, 75%) showed an improved serum creatinine (<1 mg/dL) 1 year post diagnosis/at last follow-up. In this pediatric series of AIN, TINU contributed to a large subset of cases with known etiologies. On follow up, majority of the cases demonstrated recovery of renal function.

Comprehensive analysis of clinical and laboratory features of 440 published cases of Sjögren's syndrome and renal tubular acidosis.

AIM: To describe the clinical and laboratory features of Sjögren's syndrome (SS) with renal tubular acidosis (RTA) from published literature. METHODS: A systematic search of indexed publications in all languages till December 2021 identified cases of SS with RTA (SS-RTA) and were included if either antibody (anti-SSA/anti-SSB) or salivary gland histopathology were positive. RESULTS: There were 440 cases of SS-RTA (63.9% from Asia, 95.5% women). The median (range) age was 37 (6-78) years. Only 7.7% had a previous diagnosis of SS. Oral or ocular sicca symptoms were present in 63.7%. Positive ocular tests, oral tests, anti-SSA, anti-SSB and salivary gland histopathology were reported in 256/331 (77.3%), 123/128 (96%), 382/407 (93.9%), 298/379 (78.6%), and 246/268 (91.8%), respectively. Hypokalemic paralysis (HP) was the presenting feature in 63.6%; 25% had multiple episodes of HP and 8.4% had respiratory paralysis. Type 1, type 2, combined type 1 & 2, and type 4 RTA was seen in 388, 8, 38, and 3 patients, respectively. Proximal dysfunction and RTA complications were infrequently evaluated. Fanconi syndrome, nephrogenic diabetes insipidus, proteinuria, and low estimated glomerular filtration rate were found in 45, 21, 178, and 157, respectively. Nephrocalcinosis, renal stones, and osteomalacia were reported in 92, 79, and 72, respectively. Tubulointerstitial nephritis was found in 142 out of 152 renal biopsies. CONCLUSION: SS-RTA is an early manifestation of SS characterized by younger age and subclinical sicca symptoms. Although evaluated less frequently, oral sicca signs and salivary gland biopsy have a high positive yield. HP is the most common presentation. RTA is mostly distal; proximal dysfunction and complications were infrequently assessed.

[Diagnostic and treatment difficulties in kidney damage in the patient with generalized sarcoidosis during COVID-19. Case report].

The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.

Rapidly progressive IgA nephritis and sarcoidosis.

Renal sarcoidosis frequently causes granulomatous interstitial nephritis, but clinically relevant nephritis is uncommon. IgA nephropathy caused by sarcoidosis is usually associated with milder stages of renal dysfunction, and only one case of rapidly progressive IgAN has been reported to date. We present an interesting case of a patient with a rapidly progressive form of IgA nephropathy caused by sarcoidosis that was successfully treated.  DOI: 10.52547/ijkd.7027.

Primary biliary cholangitis presenting with Fanconi syndrome: an important phenotype.

A woman in her 50s was referred to nephrology clinic due to progressive chronic kidney disease. She exhibited features of proximal renal tubulopathy, namely Fanconi syndrome, including normoglycaemic glycosuria, normal anion gap metabolic acidosis, and intermittent hypouricaemia and hypophosphataemia. Kidney biopsy showed tubulointerstitial inflammation and focal chronic damage. In addition, antimitochondrial antibodies were present and she had abnormal liver blood tests. A unifying diagnosis of primary biliary cholangitis with an associated renal tubulopathy and interstitial nephritis was made. She was commenced on sodium bicarbonate, ursodeoxycholic acid and oral prednisolone, leading to an improvement in liver biochemistry. Kidney function was stabilised, but a sustained improvement was not seen. This case acts as a reminder of the rare association of tubulointerstitial nephritis and Fanconi syndrome with primary biliary cholangitis, which may be an under-recognised phenotype.

A Rare Case of Granulomatous Interstitial Nephritis in a Patient With COVID-19.

Acute kidney injury (AKI) in patients with coronavirus disease 2019 (COVID-19) is common, especially among severely ill patients. While acute tubular necrosis (ATN) is one of the most common findings in published kidney biopsy series for patients with COVID-19 infections, a number of glomerular pathologies have been described as well. Among glomerular pathologies in COVID-19, COVID-19-Associated Collapsing Glomerulopathy (COVAN) remains the most common pattern of injury. Patients with 2 high-risk APOL1 alleles appear to be at increased risk for COVAN, similar to other forms of collapsing glomerulopathy such as HIV-Associated Nephropathy. Acute interstitial nephritis (AIN) is a less common finding in patients with COVID-19 and reported cases have been mild. Reports of a subtype of AIN, granulomatous interstitial nephritis (GIN), among COVID-19 patients are extremely rare and have not been reported in association with COVAN. Here, we report a case of COVAN associated with severe GIN.