Acute Kidney Injury: Medical Causes and Pathogenesis.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI.

A patient with dialysis-dependent acute kidney injury due to hantavirus complicated with SARS-CoV-2 infection.

In this case, we report a 64-year-old man presenting with anorexia, nausea and vomiting, mild abdominal pain, and oligoanuria for a few hours. His previous medical history included diabetes, hypertension, and chronic kidney disease (CKD) stage 3. Upon arrival, laboratory results revealed stage III acute kidney injury (AKI) with hyperkalemia requiring dialysis treatment. During hospitalization, both pre-renal and post-renal causes of AKI were excluded, and a careful diagnostic evaluation, including kidney biopsy and serology testing, revealed acute interstitial nephritis and positive IgM for hantavirus. The patient was started on steroid treatment, which led to complete recovery of kidney function over 3 months. Moreover, during his hospitalization, the patient was also diagnosed with SARS-CoV-2 infection, possibly due to intra-hospital transmission and was hospitalized at the COVID-19 Department for 14 days, eventually with no further complications. Hantavirus nephropathy should be at the differential diagnosis of AKI, even in the absence of typical symptoms. Steroid treatment may be helpful in reversal of kidney injury.

Have we missed AINything? Acute interstitial nephritis in SARS-CoV-2 infection and vaccination.

Acute interstitial nephritis (AIN), defined by the presence of interstitial inflammation accompanied by tubulitis, is an often overlooked cause of acute kidney injury (AKI). It is now well established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide variety of kidney injuries, most commonly acute tubular injury and collapsing glomerulopathy. In comparison, AIN is rarely documented in association with SARS-CoV-2 both anecdotally and in larger series of autopsy or biopsy studies. In this issue of the Journal, León-Román describe five cases of AIN in patients with a history of coronavirus disease 2019 (COVID-19) and highlight AIN as a possibly under-reported or ignored facet of renal disease associated with SARS-CoV-2. They describe three scenarios in which AIN can be seen: (i) SARS-CoV-2 infection after diagnosis of AIN, (ii) AIN followed by SARS-CoV-2 infection in the same admission and (iii) Severe SARS-CoV-2 and AIN possibly associated with SARS-CoV-2 itself. Overall, AIN remains rare in SARS-CoV-2 and causality is difficult to ascertain. Interestingly, AIN is not only seen in association with the disease itself but also with SARS-CoV-2 vaccination. This scenario is equally rare and causality is no less difficult to prove. A history of preceding SARS-CoV-2 infection and vaccination should be actively sought when patients present with otherwise unexplained AIN.

Case Report: SARS-CoV-2 Associated Acute Interstitial Nephritis in an Adolescent.

Acute interstitial nephritis (AIN) has been recently recognized as one of the infrequent kidney involvement phenotypes among adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although SARS-CoV-2 associated intrinsic kidney disease has been scarcely reported in children, only one case of AIN temporally associated with the infection has been described in the pediatric population so far. We presented a case of a 12-year old boy who presented with fatigue, anorexia, and polydipsia following an RT-PCR that confirmed SARS-CoV-2 infection seven weeks prior to admission. Initial workup revealed increased serum creatinine (235 µmol/L), glucosuria, low-molecular-weight proteinuria, mild leukocyturia, and microhematuria with hyaline and granular casts on microscopy. Antibodies against the SARS-CoV-2 S protein receptor-binding domain confirmed prior infection with high titers. Kidney biopsy showed diffuse active interstitial nephritis with negative immunofluorescence and positive immunohistochemistry for SARS-CoV-2 in the inflammatory cells within the interstitium. Electron microscopy revealed several SARS-CoV-2-like particles. Kidney function continued to deteriorate despite several days of supportive therapy only (peak serum creatinine 272 µmol/L); thus, treatment with methylprednisolone pulse-dose therapy was initiated and was followed by oral prednisolone with gradual tapering. Kidney function completely recovered after 3 weeks post-discharge and remained normal after 11 weeks of follow-up (last estimated glomerular filtration rate 106 ml/min/1.73 m2) with only residual microhematuria. Our case adds to the emerging evidence of SARS-CoV-2 as a potential etiological agent of AIN in children and also suggests that interstitial kidney injury may result from secondary inflammatory damage. Epidemiological history, serologic testing, and SARS-CoV-2 detection in biopsy should be considered in the work-up of children with AIN of unknown etiology.

Two adolescent cases of acute tubulointerstitial nephritis after second dose of COVID-19 mRNA vaccine.

The Food and Drug Administration (FDA) expanded the emergency use authorization for the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) for children aged 12-15 years on 10 May 2021. To date, less than a year has passed since vaccination against COVID-19 has been used in children and adolescents, and the overall effects and safety of these vaccines are still being assessed. The BNT162b2 vaccine originally had a favorable profile in 12-17-year-old recipients compared with older ages, and no serious adverse events had previously been reported. Despite various adverse events, the benefit of reducing the infection rate or the frequency of severe COVID-19 has been evaluated to outweigh the harm caused by COVID-19 vaccination. Additionally, several cases of sudden development of new-onset or relapsing glomerular diseases, including acute kidney injury (AKI), have been reported in adults following the BNT162b2 SARS-CoV-2 mRNA vaccine. Herein, we present two cases of adolescents who developed AKI following the second administration of the BNT162b2. These are the first pediatric cases of acute tubulointerstitial nephritis temporarily linked to SARS-CoV-2 vaccination.

[Leukocytoclastic vasculitis and acute renal failure following inactivated SARS-CoV-2 vaccine]. / Vascularite leucocytoclasique et néphrite interstitielle aiguë après vaccin à SARS-CoV-2 inactivé.

SARS-CoV-2 vaccines are being administered worldwide. Most side effects are mild and self-limiting with few reported cases of severe reactions. We report a case of leukocytoclastic vasculitis with acute kidney failure following aninactivated SARS-CoV-2 vaccine, unique for its dramatic visual presentation and its rapid response to treatment. This is the case of a 58years-old man presenting with fever, arthralgias and vascular purpura on his limbs associated with acute kidney failure requiring hemodialysis nine days after anti-COVID-19 vaccination. Skin biopsy revealed a leukocytoclastic vasculitis and a renal biopsy showed an acute tubulointerstitial nephritis. The vascular purpura resolved 7days after initiating treatment with prednisone but the patient remains in chronic renal failure. The analysis and investigation of the complications and adverse events induced by anti-COVID-19 vaccines could increase our understanding of the underlying pathogenesis.

Nephrotic syndrome and acute kidney injury following CoronaVac anti-SARS-CoV-2 vaccine.

A 67-year-old female with Type 2 diabetes mellitus developed nephrotic syndrome within 1 week of receiving the first dose of severe acute respiratory syndrome coronavirus 2 CoronaVac vaccine. A kidney biopsy was consistent with minimal change nephrotic syndrome and treatment was symptomatic with antiproteinuric therapy and improvement in proteinuria. Oedema returned within 1 week of the second dose of CoronaVac. On this occasion, acute kidney injury and massive proteinuria were noted. In kidney biopsy, glomeruli were normal, but tubulointerstitial inflammation consistent with acute tubulointerstitial nephritis was noted. Pulse followed by oral steroids was followed by recovery of kidney function. Proteinuria decreased after initiation of cyclosporine A.

A Case of Acute Interstitial Nephritis After Two Doses of the BNT162b2 SARS-CoV-2 Vaccine.

BACKGROUND: The development of vaccines to prevent COVID-19 breakouts came with highly positive results but some unexpected side effects. Rare side effects have been seen with the BNT162b2 SARS-CoV 2 vaccine. CASE PRESENTATION: We present the case of a 45-year-old female patient who developed an acute kidney injury needing urgent hemodialysis one week after the second administration of the BNT162b2 SARS-CoV 2 vaccine. She developed a macular rash on her lower limbs and palms as well. A kidney biopsy was performed 10 days after vaccine inoculation, diagnosing acute interstitial nephritis and acute tubular necrosis with cellular casts. The patient was treated with three corticosteroid pulses followed by daily prednisolone. We witnessed clinical improvement 4 days after the initial corticosteroid treatment with progressive recovery of kidney function and hemodialysis withdrawal. After 2 weeks, the patient had recovered her kidney function. Immunophenotyping was performed, diagnosing a hypersensitivity to the vaccine and the polyethylene glycol excipient. CONCLUSION: Patients may develop acute reactions to vaccines. In this case, symptoms seem to correlate significantly with its inoculation and, although this case had a favourable outcome, these side effects must be made aware for clinicians and patients.

COVID-19 Infection and Acute Kidney Injury: Cause or Complication?

Management of COVID-19 infection is the trend topic in the scientific community and case identification is a key step to contain the pandemic. While pneumonia and acute respiratory distress syndrome represent the typical severe manifestations of the disease, atypical presentations pose significant diagnostic and therapeutic challenges for physicians, especially when diagnostic tests are repeatedly negative. Clinical picture of COVID-19 patients is often complicated by bacterial infections or thrombotic events. Here, we present and discuss a case report identified in our center as example of a challenging diagnosis and 2 uncommon complications: severe hyponatremia and acute kidney injury requiring renal replacement therapy, caused by parenchymal damage and with a possible direct involvement of the virus.

Ibrutinib-induced acute kidney injury via interstitial nephritis.

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.

Characterization of acute kidney injury in critically ill patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) frequency, severity and characterization in critically ill patients has not been reported. METHODS: Single-centre cohort performed from 3 March 2020 to 14 April 2020 in four intensive care units in Bordeaux University Hospital, France. All patients with COVID-19 and pulmonary severity criteria were included. AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterization (transient versus persistent AKI; proteinuria, haematuria and glycosuria) and short-term outcomes were evaluated. RESULTS: Seventy-one patients were included, with basal serum creatinine (SCr) of 69 ± 21 µmol/L. At admission, AKI was present in 8/71 (11%) patients. Median [interquartile range (IQR)] follow-up was 17 (12-23) days. AKI developed in a total of 57/71 (80%) patients, with 35% Stage 1, 35% Stage 2 and 30% Stage 3 AKI; 10/57 (18%) required renal replacement therapy (RRT). Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median (IQR) urine protein/creatinine of 82 (54-140) (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 ± 20, indicating predominant tubulointerstitial injury. Only two (4%) patients had glycosuria. At Day 7 after onset of AKI, six (11%) patients remained dependent on RRT, nine (16%) had SCr >200 µmol/L and four (7%) had died. Day 7 and Day 14 renal recovery occurred in 28% and 52%, respectively. CONCLUSION: Severe COVID-19-associated AKI is frequent, persistent, severe and characterized by an almost exclusive tubulointerstitial injury without glycosuria.

[Renal Monomorphology in COVID-19 with Acute Renal Insufficiency]. / Nierensonomorphologie bei COVID-19 mit akuter Niereninsuffizienz.

Renal Monomorphology in COVID-19 with Acute Renal Insufficiency Abstract. A 78-year-old ventilator-dependent COVID-19 patient developed severe renal failure with an estimated glomerular filtration rate of 20 ml/min per 1.73 m2 and nephrotic proteinuria. Sonography showed echo-dense and enlarged kidneys with high resistance indices (>0.8). Echocontrast sonography showed a delayed renal perfusion. In the further course of the disease renal function recovered, kidney size decreased and the renal perfusion normalized. An acute COVID-19-associated interstitial nephritis is postulated.