Infections and the Kidney

Global infections are very frequent cause of AKI. Often this is due to the non-specific systemic effects of sepsis and volume depletion and therefore can occur with many infectious agents perhaps most searingly brought to our attention with the SARS-CoV-2 pandemic. The kidney can also be damaged by infections directly involving the renal parenchyma, because of persistent infection elsewhere in the body, as a post-infectious response and secondary diseases causing obstruction. Identifying, first, that kidney injury is due to infection and the particular infection causing the patient's presentation is critical to management. Some infections discussed in this chapter are confined to specific areas of the world, but with increasing global travel and migration, patients may present to healthcare facilities anywhere;thus, a thorough travel history is invaluable. © Springer Nature Switzerland AG 2014, 2022.

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.

Massive polyuria associated with severe COVID-19-related pneumonia complicated by pulmonary embolism

Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.

Spectrum of Indication Kidney Biopsies in Community Acquired Aki

Introduction: Community acquired acute kidney injury (CA-AKI) in low income settings is different from that in the high income settings. Infections, poisoning, toxic envenomations and pregnancy related AKI are common. Kidney biopsy is seldom performed in these patients unless atypical clinical course or features are present. We have established a prospective cohort of patients with CA-AKI at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. We present the spectrum of kidney biopsies in patients who underwent kidney biopsy in this cohort. Method(s): The study is a single centre, prospective, observational cohort study of patients with CA-AKI at PGIMER. Patients aged >12 years and with a diagnosis of CA-AKI are eligible for enrolment. Patients with underlying CKD, urinary tract obstruction, COVID 19, malignancy or heart failure are excluded. Clinical and laboratory data are recorded at baseline. Follow up visits are scheduled at 1 and 4 months after hospital discharge. Kidney biopsies are done only in those patients who have atypical clinical course or features (e.g. persistent kidney dysfunction despite other clinical improvement, strong clinical suspicion of dominant glomerular involvement or interstitial nephritis etc.). We present the spectrum of histopathological diagnoses that were recorded in such patients till date. Result(s): Till now, 646 patients have been included in the cohort. The leading causes of CA-AKI are sepsis (52%), obstetric complications (14%), envenomation (8%), nephrotoxic drugs (6%) and poisons (3%) (figure 1). 18.4% patients had died after CA-AKI. At >=3 months after CA-AKI, 16.3% patients had not recovered completely with persistent eGFR <60 ml/min/1.73m2. 44 patients had undergone kidney biopsy in this cohort. Incomplete recovery, and clinical or diagnostic dilemmas were indications for doing kidney biopsy. The leading clinical diagnoses in this subgroup were sepsis (23%), nephrotoxic drugs (23%), envenomation (9%), obstetric causes (6.8%) and others (25%). Acute interstitial nephritis, acute tubular necrosis and acute cortical necrosis were most common histologic diagnoses (table 1). Combinations of various histologic features were not uncommon. Pigment casts were recorded in 13 patients. 4 patients had acute cortical necrosis, 2 being after post-partum AKI and one each due to acute gastroenteritis and unknown animal bite. Glomerular involvement were recorded in 8 patients (table 1). Thrombotic microangiopathy was present in 4 patients. In this subgroup of patients who underwent kidney biopsy, 3 (7%) had died and 8 (18%) had eGFR <60 ml/min/1.73m2 at >=3 months. Figure 1: Causes of CA-AKI in patients [Formula presented] Table 1: Histologic diagnoses in kidney biopsies in CA-AKI cohort. [Formula presented] Conclusion(s): Acute interstitial nephritis and acute tubular necrosis, alone or in combination with other findings, were the most common histologic diagnoses in indication kidney biopsies in CA-AKI. Adverse outcomes (mortality or progression to CKD) are common after CA-AKI. No conflict of interestCopyright © 2023

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.Copyright © The Author(s) 2022.

Covid-19 Infection in Peritoneal Dialysis Patients: Epidemiological and Clinical Profile, Risk Factors and Mortality

Introduction: Since the beginning of the coronavirus infection 2019 (COVID-19) pandemic, the population of dialysis patients has been recognized as a population at high risk of infection due to immune background and comorbidities. This study aims to describe the epidemiological characteristics, mortality and risk factors for COVID-19 infection in this population. Study design: Retrospective cohort study Methods: Patients on peritoneal dialysis in a university hospital center tested positive for coronavirus-19 by PCR method by nasopharyngeal swab from January 2020 to June 2022. Epidemiological and medical data collected from computerized medical records and from the Registry of French language peritoneal dialysis. Analytical approach: Logistic regression analyzes conducted to identify epidemiological and clinical characteristics associated with COVID-19 and risk factors associated with COVID-19 infection Results: 21 (31.8%) patients on peritoneal dialysis developed COVID-19. The male sex was slightly predominant with 11 men (52.4%). The average age of the patients was 67.48 years +/- 16.48, the average body mass index of the patients affected was 24.26, the average length of seniority in dialysis of the patients was 2.54 years +/- 1.3 years. The predominant initial nephropathy was diabetic nephropathy, glomerulosclerosis, IgA nephropathy and interstitial nephropathy with rates of 38.1%, 19%, 9.5% and 9.5% respectively. The risk factors for covid infection found were: an antecedent of ischemic cardiopathy, the diabetic nephropathy Conclusion(s): While it is true that Sars-cov 2 infection and its complications have increased the mortality rate in most dialysis centres, it should be noted that other factors have contributed to the increase in mortality such as socioeconomic circumstances related to financial financial difficulties, missed consultation appointments secondary to the apprehension of contracting the disease while traveling to the centers as well as the difficult due to confinement. No conflict of interestCopyright © 2023

Granulomatous Interstitial Nephropathy : When the Kidney Spills the Bean

Introduction: Sarcoidosis is a rare granulomatosis. The absence of well-defined criteria for definition and the existence of differential diagnosis makes the positive diagnosis difficult. Method(s): We report a case of sarcoidosis that illustrates the difficulty of this diagnosis in the presence of atypical clinical manifestations and a strong suspicion of tuberculosis. Ultimately, renal histology allowed the positive diagnosis and the response to corticosteroids confirmed it retrospectively. Result(s): Our patient was a 66 years-old female with a history of hypertension who presented with a sensory and motor polyneuropathy a couple of months after a mild COVID-19 pneumonia, hospitalized for exploration of a worsening renal function due to a tubulointerstitial neuropathy (creatinine upon admission at 250 micromol/l, eGFR = 16 ml/min/1,73m2 -MDRD). Kidney biopsy revealed an interstitial infiltrate of monocytes and fibrosis alongside non-necrotic and giant-cell epithelioid interstitial granulomas. Extra-renal signs consisted of the above-mentioned neuropathy, bilateral mediastinal adenopathies with no signs of a pulmonary disease at the bodyscan, a hepatomegaly, splenomegaly, a pleural and pericardial effusion of low abundance, and a peritoneal thickening. Bronchoscopy and bronchoalveolar washing found no evidence for malignancies and screening for mycobacterial infections by polymerase chain reaction was negative. No granulomas were found at the hepatic biopsy. Digestive tract endoscopy and biopsies showed no abnormalities. During hospitalization, the patient presented an episode of acute polyradiculonevritis confirmed by cerebral-spine fluid study and nerve conduction study results. Our patient received intraveinous immunoglobulins (IgIV) with a favorable outcome but relapsed one month later, showing signs of respiratory failure. Upon the second relapse of the chronic polyradiculonevritis and based on the absence of bacteriological and histological evidence for a mycobacterial infection and the results or the renal biopsy, the patient received high-dose corticosteroids alongside a second course of IgIV. The neuropathy regressed totally within a month with a decrease of creatinine level to 140 micromol/l (eGFR = 35ml/min/1,73m2) alongside the polyserositis and organomegaly. The final diagnosis was that of a sarcoidosis with pulmonary and renal involvement. Although the neuropathy could be considered a manifestation of sarcoidosis, its origin was intricated as post-viral original could not be formally excluded. Conclusion(s): The etiological diagnosis for granulomatous interstitial nephropathies can be challenging due to similar clinical presentations and the need to start specific treatments especially in the presence of life-threatening situations and the absence of clear criteria defining sarcoidosis further enhances the level of difficulty. No conflict of interestCopyright © 2023

Finding an Answer for an Adolescent with Back Pain

Case report - Introduction: This is the case of an adolescent referred to rheumatology following 5 years of back pain. After years of trying a number of treatments without much success, the cause was found to be a previously undiagnosed urological pathology. The case highlights awareness of non-rheumatological causes and incidental findings which can redirect a patient towards more appropriate treatment and reduce the potential for long-term adverse health issues and anxiety. Case report - Case description: B was referred age 16 to rheumatology with a 5-year history of lower back pain. She had previously seen paediatricians with symptoms initially attributed to constipation due to intermittent straining and hard stool. However, constipation remedies had not relieved the pain which progressed gradually to a more persistent dull ache with impact on daily activities. Various analgesics (including paracetamol and non-steroidal anti-inflammatories), exercises and acupuncture had not helped. There was no history of recurrent urinary tract infections or symptom correlation with fluid intake, menstruation or bowel habit. No inflammatory features or connective tissue disease symptoms were noted and family history was unremarkable Clinical examination was normal apart from mild tenderness in the lumbar region. Rheumatoid factor was borderline positive (15 iu/mL) with the rest of blood tests normal including renal function, inflammatory markers (CRP, ESR), anti CCP and ANA. She had minimal microscopic haematuria without proteinuria. MRI spine in 2015 was normal. In view of her young age and symptoms affecting daily activities, STIR sequence spinal MRI was requested. This excluded any new or old inflammatory changes but incidentally identified a dilated left pelvi-calyceal system. Renal ultrasound confirmed a grossly hydronephrotic left kidney with hydroureter and minimal renal tissue suggesting longstanding obstruction. No calculi were seen. The patient was referred to urologists. Further investigations (including MRI abdomen) confirmed similar findings and a distal ureteric stricture. A MAG 3 renogram showed a normal right kidney but only 12% functioning of the left kidney. Urologists have advised surgery (removal of left kidney and ureter) which may relieve symptoms or a conservative non-surgical approach (continue analgesia, physiotherapy and monitoring). The patient and her family are relieved to have a possible cause identified and are considering the surgical option due to ongoing flank discomfort. Case report - Discussion: This was an interesting finding of hydroureter and hydronephrosis causing longstanding back pain presenting to rheumatologists. Until completion of the spondyloarthropathy protocol MRI (STIR images), aetiology had been unclear. Hydronephrosis and hydroureter has no specific age or racial predilection. Signs and symptoms may depend on whether obstruction is acute/chronic. Chronic cases may be asymptomatic or present as a dull discomfort (like this case). Some cases may only present in adulthood with pain precipitated by fluid intake. Blood tests may show impaired kidney function. Post-mortem studies suggest 50% of people have at least one renal abnormality (e.g., renal cysts, duplex ureters) with autopsy series incidence of hydronephrosis reported as 3.1%. Causes include anatomical abnormalities such as vesico-ureteric reflux, urethral strictures (usually present in childhood), calculi, benign prostatic hyperplasia, or intrapelvic neoplasms, pregnancy and infections (e.g., TB). Sudden onset unilateral renomegaly was reported in one case of primary Sjogren's with lymphocytic interstitial nephritis and positive Sjogren's autoantibodies. Our patient has no clinical or serological evidence of connective tissue disease. Minor pelvi-calyceal distension can occur as a normal finding in wellhydrated patients and pregnancy. However, significant hydronephrosis requires assessment to determine cause as it may affect long term renal function. Imaging via computed tomography, ultrasound and urograms can help guide further management. In this case the preceding cause and duration of pathology is unknown. Sterile, giant hydronephrosis treatment options include observation and ureteric stent or nephrostomy in patients unfit for surgery. Nephrectomy is advised for pain and recurrent infection in a non-functioning kidney. Complications may include bowel perforation, vascular injury and urine leakage. Both open and minimally invasive procedures have good reported outcomes. The COVID-19 pandemic and exams have affected timing of any elective procedures and the patient understands surgery may or may not offer complete symptom resolution. Case report - Key learning points: . Non-inflammatory causes of back pain should always be considered in cases of persistent back pain, particularly in young people to ascertain if there is a treatable cause . Hydronephrosis cases can be asymptomatic or present with vague, intermittent, non-specific abdominal symptoms with normal physical examination with or without haematuria. This can cause diagnostic uncertainty and delay referral to urology and appropriate renal investigations . Assessment of renal function (including MAG 3 renogram) is important to guide further management . Surgical interventions (pyeloplasty/nephrectomy) may ease symptoms long term but there is no guarantee of a successful outcome and operative risks need to be considered too . Left undiagnosed, potentially this patient could have had further disruption to daily activities and both physical and mental well being.

Acute Kidney Injury and Acute Renal Failure in Coronaviral Infection

In December 2019 a newly described single-stranded coronavirus, later named SARS-CoV-2, started its expansion around the world and subsequently caused a global pandemic, affecting the lives of millions of people worldwide. SARS-CoV-2 can bind multiple receptors on different cells and thus invade many target organs, including the respiratory and gastrointestinal mucous membranes, lungs, central nervous system, heart, etc. This virus can affect the kidney tissue both directly and as a consequence of other organ involvement or of the treatment administered, causing acute kidney injury and leaving long term squeals that worsen the prognosis. We describe three patients with acute kidney injury and subsequent acute renal failure at the background of coronaviral infection. Copyright © 2022 M. Nikolova et al., published by Sciendo.

[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.

ACUTE INTERSTITIAL NEPHRITIS AS A PRIMARY PRESENTATION OF CANDIDA INFECTIVE ENDOCARDITIS

Introduction: Acute Interstitial Nephritis (AIN) is an important cause of Acute Kidney Injury (AKI), and infections are the second most common etiology, after the drugs. However, AIN following fungal infections is rare. We describe two cases of AIN, which on the investigation turn out to be candidemia following fungal infective endocarditis. Methods: CASE 1: A 65-year-old man with hypertension and diabetes without diabetic or hypertensive retinopathy and prior normal renal function, presented to us with vague abdominal pain with steadily creeping creatinine to 2mg/dl within 2 weeks, and urine showed no albuminuria and sediments. There was no history of any specific drug intake. His hematological and other parameters were normal. Blood and urine cultures were sterile. He underwent a renal biopsy which revealed acute interstitial nephritis (Figure 1). He was started on prednisolone at 1mg/kg/day for 1-week following which he had a rapidly worsening azotemia requiring hemodialysis. Steroids were stopped. Repeat blood cultures were sent which grew candida albicans resistant to flucytosine. Re-evaluation of the fundus revealed macular infarct in the right eye with vitreoretinitis in the left eye suggestive of endophthalmitis. PET CT showed increased FDG uptake in both kidneys suggestive of pyelonephritis. Trans-esophageal echocardiography (TEE) showed aortic valve vegetations. He was treated with antifungals for 3 months. He was dialysis-dependent for 2 weeks. He gradually regained normal renal function 3 weeks after starting anti-fungal agents. CASE 2: A 57-years-old man with diabetic, hypertensive, and no diabetic retinopathy had severe covid pneumonia in June 2021 requiring oxygen and tocilizumab 80 mg for 4 days, recovered with normal renal function. He presented to us 1 month later with unexplained non-oliguric severe AKI requiring dialysis, with bland urine sediments. Renal biopsy showed lymphocytic infiltrates in the interstitium suggestive of AIN (Figure 2). Blood cultures were sterile, but serum beta-D-glucan was elevated at 333 pg/ml. He was Initiated on 1mg/kg of prednisolone, on the presumption of drug-induced AIN. Simultaneously workup for systemic infection revealed mitral anterior leaflet endocarditis. He was initiated on anti-fungal therapy on the advice of an infectious disease specialist and the steroid was stopped. He continued to be dialysis-dependent after 6 weeks, despite anti-fungal agents. Results: [Formula presented] Conclusions: AIN contributes a significant proportion of cases in unexplained AKI. Prompt evaluation with a renal biopsy is warranted. Acute interstitial nephritis particularly due to candidemia can be oligosymptomatic as seen in our two cases. Since steroids have a significant role in treating early AIN, a dedicated search for underlying silent endocarditis and candidemia is advisable before initiating steroid therapy. Ophthalmic fundus evaluation, TEE, and repeat blood culture may be necessary to identify hidden candidemia. We recommend an evaluation to exclude fungal endocarditis in patients with AIN who present with minimal or no symptoms and no definitive cause for AIN is present. No conflict of interest

Prompt Diagnosis and Intervention of Oxalate Nephropathy to Salvage Kidney Function

Hyperoxaluria can be primary due to defective glyoxylate metabolism leading to hepatic oxalate overproduction or secondary due to increased intestinal oxalate absorption. Oxalate nephropathy is the deposition of calcium oxalate crystals leading to tubular injury, interstitial fibrosis, and AKI or CKD. This describes three cases of renal oxalosis. First is a 60 year old male with stroke, hypertension, diabetes who presented with AKI of 4.5 mg/dL from 1.6 that rose to 11 mg/dL. Serologies for glomerulonephritis and paraproteinemia were negative. Biopsy showed tubular oxalate crystal deposition with tubular injury and interstitial nephritis. His renal failure required dialysis. Second is a 58 year old female with gastric bypass surgery who presented for edema and AKI from 1.3 to 3.6 mg/dL. Serologies were also negative. Biopsy showed interstitial nephritis with tubular calcium oxalate deposition. She was started on prednisone 60 mg. Creatinine stabilized to 2.2 mg/dL, not requiring dialysis. Third is a 82 year old male with obesity and sarcoma of the scalp treated with pembrolizumab who presented with dyspnea, edema and an AKI from 1 to 8.6 mg/dL. Urine sediment was bland with negative serologies. Differential included AIN due to pembrolizumab. Patient was started on high dose prednisone and biopsy showed interstitial nephritis and calcium oxalate crystal deposition. Patient endorsed taking frequent vitamin C as prophylaxis for Covid. Creatinine stabilized to 2.9 mg/dL not on dialysis. Classic etiologies of hyperoxaluria include dietary oxalate from ascorbic acid and fat malabsorption from gastric bypass surgery. Treatment includes increased fluid intake, oral calcium supplements and low oxalate diet. Oxalate nephropathy remains an under recognized cause of kidney failure, as such, early biopsy and intervention are necessary. (Figure Presented)

Indium 111 White Blood Cell Scan to Diagnose Acute Interstitial Nephritis

Drug- Induced Acute Interstitial Nephritis is a known cause of AKI commonly caused by NSAIDS, PPI and antibiotics which have been well documented in the literature. The hallmark presentation is fever, rash and eosinophilia, although this is only seen in a minority of cases. Half of cases do not present with AKI and therefore the clinician must have a high index of suspicion for further workup. Early detection can lead to early treatment which should result in improved outcomes. 67 Gallium renal scan Scintigraphy has been used over the last 30 years to help diagnose AIN, however no known use of Indium-111 WBC Scan has been used to in the diagnosis of AIN. A 71-year-old male presented with fevers and generalized weakness for 4 days, endorsing associated paresthesias in both lower extremities as well as visual hallucinations. After a primary care physician outpatient visit, a WBC Scan showed localization to bilateral kidneys and the colon. He was sent to the hospital for IV antibiotics as bilateral pyelonephritis was suspected. Initial labs was significant for WBC of 11.4k (without Eosinophilia), serum creatinine of 1.73 (Baseline 1.1). Urinalysis was negative for infection however with trace proteinuria. Covid test was negative. Three sets of blood cultures were negative. Imaging was negative for acute pathology. IV antibiotics were started without resolution of symptoms. Transthoracic Echo was negative for any vegetations. Patient continued to have fevers. He stated that he was started on hydralazine three weeks prior to admission. After cessation of Hydralazine he ceased to have fevers. Case was discussed with Radiology and he had a renal biopsy. Biopsy results confirmed mild AIN, 45% global sclerosis, severe arterial and arteriolar sclerosis, tubular atrophy and interstitial fibrosis. He was started on Prednisone and tapered over 2 months. Renal function returned to baseline. AIN was suspected because of recent initiation of Hydralazine even though neither rash nor eosinophilia was present. A positive Indium-111 WBC Scan in the setting of fever, AKI and elevated WBC count encouraged us to proceed with the biopsy even though the patients' AKI had “resolved.” Here we aim to show that Indium-111 WBC assisted in the diagnosis of AIN and could be used in the future for clinicians as an indication for biopsy.

Relapse of Membranous Nephropathy and Renal Sarcoidosis Following Exposure to SARS-CoV-2 Vaccine (Johnson & Johnson)

The role of infectious agents derived antigens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as a trigger for development of autoimmune mediated disorders following natural infection or immunization. However, there is a scarcity of reports of occurrence of autoimmune associated kidney disorders or flare ups following exposure to a SARS-CoV-2 vaccine. A 65-year-old female presented to a nephrology clinic for evaluation of worsening renal dysfunction. The patient is well known to have systemic sarcoidosis under complete remission on low dose prednisone and likely membranous nephropathy (no previous kidney biopsy) with mildly elevated phospholipase A2 receptor (PLA2R) antibodies. Her membranous nephropathy was in partial remission on angiotensin receptor blockage, with urine to protein creatinine ratio (UPCR) of 1.5 g/g . Five months after receiving the single dose SARS-CoV-2 vaccine (Johnson & Johnson®), she started having a flare up of her systemic sarcoidosis with worsening joint, skin and respiratory symptoms. Blood chemistry revealed worsening renal dysfunction with elevated creatinine up to 1.7 mg/dL from her baseline of 1.0 mg/dL. UPCR was also elevated at 3.4 g/g. Urine sediment revealed no red blood cells or casts, only several calcium oxalate dihydrate crystals. A kidney biopsy was performed and showed a combination of membranous nephropathy (PLA2R positive) along with granulomatous interstitial nephritis with well-formed epithelioid granulomas characteristic of sarcoidosis. She was started on high dose prednisone and her renal function improved to 1.2 mg/dL, UPCR decreased to 1.8 g/g and serum PLA2R antibodies became undetectable. She is still being monitored. After many years of renal sarcoidosis and membranous nephropathy remission, the relapse of renal disease after receiving the SARS-CoV-2 vaccine (Johnson & Johnson®) suggests the association between receiving the vaccine and the recurrence of renal sarcoidosis and membranous nephropathy.

Atypical Presentation of Cocaine-Induced Thrombotic Microangiopathy

Cocaine is one of the most used illicit drugs. Cocaine induced toxicity can result in hepatotoxicity, pulmonary toxicity, and renal dysfunction. Acute kidney injury (AKI) is an emergent complication in cocaine abusers. Rhabdomyolysis and vasoconstrictions mechanism are well known cause of AKI, cocaine induce thrombotic microangiopathy (TMA) is rarely reported. Cocaine is widely used in the United States, we report a case of Cocaine induced TMA in a cocaine abuser. We chronicle a case of a 42-Year-old male cocaine abuser, who presented to ED with complaints of Dyspnea, cough, anorexia and chest tightness for two days. He attributed to inhaling ammonia from cat urine along with cocaine abuse. No prior history of kidney disease or any other chronic illness. On examination, the patient appeared malnourished and cachectic. He was normotensive, lethargic and oriented. There were crackles at the lung bases. Blood tests revealed serum creatinine 18.0 mg/dL, blood urea nitrogen 150 mg/dL, hemoglobin 8.2 g/dL, platelets 173000/mm3, Retics count 8 %, LDH 1120 (84–246 IU/L) and haptoglobin < 8 (30–200mg/dL). A blood film revealed occasional schistocytes. Urinalysis showed proteinuria and microscopic hematuria. Urine toxicology revealed cocaine. Routine blood and urine cultures showed no growth. Serologic tests showed reduced complement C3 level of 40 (82-185 mg/dL) and normal C4 level of 32 (10–53mg/dL). There were no antibodies against HIV 1/2 and Covid 19. His ADAMTS-13 results showed 0.61 and 0.63 (0.68 to 1.63). Renal Ultrasound was unremarkable. Patient was intubated and ventilated in ICU;he was initiated on hemodialysis. He was provided four sessions of plasma exchanges till his ADAMTS-13 result came back near normal that was indicative of Cocaine induce TMA. Cocaine abuse is a global issue with increasing number of cases in the USA. It can cause AKI due to well-known etiologies like Rhabdomyolysis, Vasculitis, Acute interstitial Nephritis and Renal Infarction. However, Clinicians and nephrologists should also consider rare causes like TMA as a possible differential cause of AKI in the setting of cocaine abuse.

AND KIDNEY OF MALE ALBINO RATS

As a result of the scale of the Covid 19 pandemic that launched from China in December 2019 and to limit its spread, several treatments were used to control this virus, including, hydroxychloroquine, favipiravir, lopinavir, remidesivir, tocilizumab, and anakinra. Favipiravir is an antiviral drug that works by inhibiting RNA-dependent RNA polymerase, favipiravir inhibited viral genome replication, which was most noticeable in the middle of the viral proliferation period. Favipiravir was found to have antiviral activity, Purine nucleosides or purine bases inhibit favipiravir, meaning that it competes with purine nucleosides rather than pyrimidine nucleosides, In a time-of-drugaddition test, to treat a variety of RNA viruses (influenza, West Nile, yellow fever, flaviviruses, arenaviruses, bunyaviruses and alphaviruses). Here, we show for the first time the histologycal effect of favipiravir on the liver and kidneys using albino rats, using light microscopy, where the optical microscopic revealed that normal doses in liver showed hepatic cords arranged, normal central vein and mild sinusoildal infiltration of mono nuclear leukocytes mainly lymphocytes, the hepatocytes showed mild granular cytoplasm while double doses showed little hemorrhagic foci and disarrangement of hepatic cords. The magnified sections revealed few of hepatocytes showed mild cloudy swelling associated with little figures of cellular necrosis. As for kidneys, the optical microscopic observations showed multiple foci of hemorrhage, the magnified section revealed congestion of glomerular capillary tuft and few of renal tubules showed mild granular or vacular degeneration. On the other hand, sections of renal medulla revealed normal appearance for normal doses while renal cortex and medulla were showed marked interstitial nephritis, which characterized by interstitial thickening due to infiltration of mono nuclear leukocytes and the renal tubules showed sever vacular degeneration and necrosis for double doses. These results can guide the safe use of favipiravir and reduce the risks to tissue the liver and kidney by using double doses.

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.