Renal cortical necrosis - a rare manifestation of dengue fever: A case report.

RATIONALE: Dengue fever is a widespread mosquito-borne viral disease, most prevalent in the tropical and subtropical areas of the world. There has been a significant rise in the incidence and number of outbreaks of dengue in recent years, which has made it a matter of global concern. It may be associated with a number of renal complications, ranging from hematuria, proteinuria, glomerulonephritis, and acute tubular necrosis. However, renal cortical necrosis (RCN) is a rare renal complication of this disease. PATIENTS CONCERNS: We report the case of a young gentleman who presented with fever, vomiting, and anuria. On workup, he was found to be having complicated Dengue fever with RCN resulting in acute renal failure. DIAGNOSIS: To the best of our knowledge, RCN is not a reported renal complication of dengue fever. INTERVENTIONS AND OUTCOMES: Our report highlights the importance of early consideration of renal cortical necrosis in patients with dengue fever and persistent anuria. LESSON: This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

Pathologic Correlation with Renal Dysfunction after Intravitreal Injections of Vascular Endothelial Growth Factor Antagonists.

OBJECTIVE: Vascular endothelial growth factor (VEGF) antagonists have been used for treating metastatic neoplasms. It has also been known that one of its side effects is to cause proteinuria and renal failure in the setting of thrombotic microangiopathy (TMA). The underlying mechanism is likely due to the inhibition of VEGF production in podocytes, resulting in diffuse fusion of foot processes and impaired glomerular endothelial fenestrations, and leading to massive proteinuria and subsequent glomerular endothelium injury. Intravitreal injection of VEGF antagonists (IIVA) has been also used to treat macular degeneration and diabetic retinal neo-vascular proliferation. The majority of patients tolerate the treatment well. However, IIVA can lead to renal dysfunction including proteinuria and gradual renal failure as a rare side effect. The goal of this study was to report two cases related to the nephrotoxicity of IIVA and review the literature associated with this topic. CASE REPORT: The first diabetic patient had elevated serum creatinine at 3.25 mg/dl and proteinuria/creatinine ratio at 6.1 after 48-month treatment of IIVA. The first renal biopsy revealed thrombotic microangiopathy that was correlated with his increased serum creatinine and nephrotic range of proteinuria. The second diabetic patient had increased serum creatinine up to 1.89 mg/dl but low proteinuria. The second biopsy showed acute tubular necrosis that was correlated with his elevated serum creatinine. CONCLUSION: Intravitreal injection of VEGF antagonist can be associated with thrombotic microangiopathy and acute tubular necrosis, leading to renal dysfunction.

Bilateral acute renal cortical necrosis after a dog bite: case report.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats' normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a "reverse rim sign" in contrast-enhanced computed tomography on hospital admission. CASE PRESENTATION: We report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs. CONCLUSION: We present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis - was visible as "reverse rim sign" on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

COVID-19-associated collapsing glomerulopathy: a report of two cases and literature review.

Nephrotic range proteinuria has been reported during the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). However, the pathological mechanisms underlying this manifestation are unknown. In this article, we present two cases of collapsing glomerulopathy (CG) associated with acute tubular necrosis during the course of COVID-19, and review the literature for similar reports. In our two cases, as in the 14 cases reported so far, the patients were of African ancestry. The 14 patients assessed had an APOL1 high-risk genotype. At the end of the reported period, two patients had died and five patients were still requiring dialysis. The 16 cases detailed in the present report strongly argue in favour of a causal link between SARS-CoV-2 infection and the occurrence of CG in patients homozygous for APOL1 high-risk genotype for which the term COVID-associated nephropathy (COVIDAN) can be put forward.

Cyclophilin Inhibition Protects Against Experimental Acute Kidney Injury and Renal Interstitial Fibrosis.

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochondrial-dependent cell death. This study investigated the therapeutic potential of a selective cyclophilin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment significantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.

Bilateral renal cortical necrosis in a child with acute pancreatitis.

Bilateral renal cortical necrosis (RCN) as a cause of acute kidney injury is very rare in the pediatric population. Progression to end-stage renal disease is seen virtually in every patient with RCN. There are many causes for the occurrence of cortical necrosis in children, with severe pancreatitis being a rarity. In this report, we describe a child with severe acute pancreatitis complicated by bilateral RCN.

Renal Cortical Necrosis; Five Consecutive Cases within Short Span of Time.

Renal cortical necrosis (RCN) is characterized by patchy or diffuse destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients of AKI. In contrast, the incidence of RCN is higher in developing countries ranging from 6%-7%. Obstetric complication is the main cause of RCN, earlier it was about 20%-30% which has been declining to 5% in the Indian subcontinent during the past two decades. The aim of this study is to review five consecutive cases of RCN diagnosed within very short span of time. Histopathologically, diagnosed five cases of RCN during one-month span in September 2016 at Armed Forces Institute of Pathology, Dhaka were included in this study. All the cases were referred cases from a tertiary level obstetric center of Dhaka city; the mean age was 24.2 ± 3.4 years. All the cases had the history of postpartum hemorrhage followed by septicemia. They all presented with acute renal failure dependent on hemodialysis for >21 days. On histological examination, three (60%) had patchy RCN and two (40%) had diffuse RCN. Two (40%) showed coagulative necrosis of all the glomeruli, two (40%) showed coagulative necrosis of >50% of glomeruli, and in one (20%) case necrosis of about 25% of glomeruli. One of the glomeruli showed global sclerotic change of most of the glomeruli. In all the cases, interstitium showed moderate focal lymphocytic infiltration and mild edema. Among all, one (20%) was found with immunoglobulin A nephropathy as an associated diagnosis. RCN is still encountered as an obstetric complication in our setting and this type of grave consequences should be prevented by better monitoring of pregnancies.

Acute kidney injury due to acute cortical necrosis following vivax malaria.

Malaria is a parasitic infection of global importance but has a high prevalence in the developing countries. Renal failure is a common complication of severe Plasmodium falciparum malaria and has been reported in up to 40% of all cases. Acute kidney injury (AKI), however, is not commonly associated with Plasmodium vivax infection. In those patients who develop AKI following P. vivax infection, the cause is commonly attributed to mixed undiagnosed falciparum infection or coexistent sepsis, dehydration, or hypotension. Infrequently, an association of P. vivax infection with thrombotic microangiopathy (TMA) has been reported. The purpose of this report is to describe renal failure due to TMA following malaria caused by P. vivax. A 24-year-old female presented with a history of fever and jaundice of two weeks duration followed by progressive oliguria and swelling of the face and feet five days after the onset of fever. The evaluation revealed normal blood pressure, anemia, thrombocytopenia, azotemia, unconjugated hyperbilirubinemia with mildly elevated transaminases, and elevated lactate dehydrogenase. Peripheral smear was positive for P. vivax, and schistocytes were seen. She was given intravenous artesunate followed by oral primaquine for 14 days. Urine examination showed proteinuria and microscopic hematuria. She remained oliguric and dialysis dependent, and her kidney biopsy revealed patchy cortical necrosis involving 40% of sampled cortex with widespread fibrinoid necrosis of the vessel wall, red blood cell fragmentation, and luminal thrombotic occlusion. Hemodialysis was discontinued after three weeks when there was the improvement of renal function over time, and her serum creatinine decreased to 2.2 mg/dL by six weeks. Patients with P. vivax malaria developing renal failure may have TMA. Renal biopsy, if performed early in the course of the disease, may identify TMA and institution of plasma exchange in such patients could help in early recovery.

[Renal cortical necrosis after application of tranexamic acid in peripartal hemorrhage]. / Renale Rindennekrose nach Gabe von Tranexamsäure bei geburtsassoziierter Blutung.

HISTORY: A 28-years old patient delivers a daughter by primary caesarian section (41. WOP) in breech presentation after a complication-free pregnancy except increased blood pressure readings at the morning of caesarian section. During the caesarian section a major bleeding of the atonic uterus with hemorrhagic shock appears. Haemostasis is achieved by mechanical tamponade, the application of red blood cell concentrates and the substitution of clotting factors, also tranexamic acid. Because of an anuric renal failure due to the shock hemodialysis is initiated. EXAMINATIONS/FINDINGS: Clinical examination and blood tests show the constellation of a thrombotic microangiopathy. There are no hints for a thrombotic thrombocytopenic purpura (TTP) or a hemolytic-uremic syndrome (HUS). In addition, a genetic testing gives no hints for an atypical HUS. After 4 weeks of dialysis duty a renal biopsy is performed. The renal biopsy shows a partly reversible tubular damage with an older ischemic cortical necrosis. DIAGNOSIS/THERAPY: In the further course the resumption of the diuresis can be observed. The dialysis treatment has to be continued because of an insufficient excretory renal function. Fortunately a living-donor kidney transplantation (mother) can be carry out successfully already one year after the hemorrhagic shock. CONCLUSION: The combination of peripartal bleeding with hemorrhagic shock, possibly aggravated by (pre-)eclampsia or HELLP-syndrome, and the application of tranexamic acid with its prothrombotic effect seems to be responsible for the major renal cortical necrosis.

Bilateral renal cortical necrosis following acute pancreatitis - A rare complication of a common disease.

Acute renal cortical necrosis is a rare cause of intrinsic acute kidney injury (AKI) which is commonly associated with obstetric complications such as placental abruption and some serious systemic disorders such as hemolytic-uremic syndrome, sepsis, severe burns, and snake bite. Acute pancreatitis is an extremely rare cause of renal cortical necrosis, and only less than 10 cases are reported in the literature. Here, we present a 24-year-old male presented with features of acute pancreatitis and oliguric AKI. His pancreatic enzymes were above 1000 IU/mL at admission. He was initiated on hemodialysis. Percutaneous renal biopsy done at 4th week of illness showed features of diffuse renal cortical necrosis. Contrast-enhanced computed tomography demonstrated hypoattenuation of cortex compared to medulla consistent with renal cortical necrosis. He developed complications such as acute necrotic collection, pleural effusion and retinal detachment in addition to renal cortical necrosis which was managed conservatively. Since there was no improvement in the renal function now, he is being evaluated for renal transplantation.

Patterns of renal involvement in a cohort of patients with inflammatory bowel disease in Egypt.

BACKGROUND AND STUDY AIM: Renal complications are frequent extraintestinal manifestations in inflammatory bowel disease (IBD). We aimed in our study to describe the spectrum of renal affection in our IBD patients. PATIENTS AND METHODS: This study is a retrospective analysis of renal biopsies done for IBD patients who developed renal diseases, at Cairo University Hospital, from June 2005 to Jan. 2016. Results : Among 896 IBD patients, 218 patients (24.3%) developed renal affection. The onset of renal disease mandated renal biopsy at 5.6 ± 7.4 years after IBD diagnosis. Nephrotic range proteinuria was the most common indication for a renal biopsy [81 (37.15%) patients]. Amyloidosis was the most common renal pathological diagnosis [56 patients (25.7%)] followed by immunoglobulin A (IgA) nephropathy [35 patients (16.1%)], focal segmental glome- rulosclerosis (FSGS) [32patients (14.7%)], crescentic glomerulonephritis (CGN) [32 patients (14.7%)], membranous nephropathy (MN) [18 patients (8.25%)], minimal change disease [17 patients (7.7%)], chronic interstitial nephritis (CIN) [10 patients (4.6%)], acute tubular necrosis (ATN) [8 patients (3.7%)], thrombotic microangiopathy (TMA) [6 patients (2.75%)], and acute interstitial nephritis (AIN)[4 patients (1.8%)]. Variable renal histopathology diagnoses did not correlate with age, duration of IBD diagnosis, or drugs used for IBD treatment. Crescentic GN was significantly correlating with ASCA, ANCA-p, and ANCA-c in serum. CONCLUSION: Amyloidosis is a common renal pathological diagnosis in our patients, and is followed by IgA nephropathy, and FSGS.

Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI.

Severe AKI is often associated with multiorgan dysfunction, but the mechanisms of this remote tissue injury are unknown. We hypothesized that renal necroinflammation releases cytotoxic molecules that may cause remote organ damage. In hypoxia-induced tubular epithelial cell necrosis in vitro, histone secretion from ischemic tubular cells primed neutrophils to form neutrophil extracellular traps. These traps induced tubular epithelial cell death and stimulated neutrophil extracellular trap formation in fresh neutrophils. In vivo, ischemia-reperfusion injury in the mouse kidney induced tubular necrosis, which preceded the expansion of localized and circulating neutrophil extracellular traps and the increased expression of inflammatory and injury-related genes. Pretreatment with inhibitors of neutrophil extracellular trap formation reduced kidney injury. Dual inhibition of neutrophil trap formation and tubular cell necrosis had an additive protective effect. Moreover, pretreatment with antihistone IgG suppressed ischemia-induced neutrophil extracellular trap formation and renal injury. Renal ischemic injury also increased the levels of circulating histones, and we detected neutrophil infiltration and TUNEL-positive cells in the lungs, liver, brain, and heart along with neutrophil extracellular trap accumulation in the lungs. Inhibition of neutrophil extracellular trap formation or of circulating histones reduced these effects as well. These data suggest that tubular necrosis and neutrophil extracellular trap formation accelerate kidney damage and remote organ dysfunction through cytokine and histone release and identify novel molecular targets to limit renal necroinflammation and multiorgan failure.

Aminoaciduria Caused by Fanconi Syndrome in a Heifer.

A case study of renal tubular dysfunction consistent with idiopathic Fanconi syndrome is reported in an 18-month-old Holstein heifer. The clinical, biochemical, and histopathological features are described. The heifer had clinical signs of growth retardation, wasting, and persistent diarrhea. Biochemical blood analysis identified hypokalemia, hyponatremia, and hypochloremia. Urinalysis identified glycosuria, proteinuria, and acidic pH. Histological examination of the kidney disclosed mild tubular necrosis with proteinaceous casts in the lumina of renal tubules. We performed LC-HRMS on urine to confirm Fanconi syndrome. Using this technique, we identified severe generalized aminoaciduria suggestive of idiopathic renal Fanconi syndrome in this heifer.

Purtscher's retinopathy and renal cortical necrosis: two rare vaso-occlusive complications in a patient with acute pancreatitis: a case report.

BACKGROUND: Purtscher's retinopathy and renal cortical necrosis are two rare vaso-occlusive complications of acute pancreatitis. Purtscher's retinopathy causes sudden impairment of vision, which was first reported in a patient with head trauma. Subsequently, it was also reported as a complication of acute pancreatitis and few other clinical conditions. Acute pancreatitis also rarely causes renal cortical necrosis leading to acute kidney injury. However, the simultaneous presence of both complications is rarely reported. CASE PRESENTATION: A 20-year-old Bengali man presented to our hospital with a history of acute upper abdominal pain, vomiting, anuria, and disorientation. He was ultimately found to have bilateral complete blindness due to Purtscher's retinopathy and acute kidney injury due to renal cortical necrosis, as sequelae of acute pancreatitis. He became dialysis-dependent, his vision did not recover, and he died 16 months after diagnosis. CONCLUSIONS: This case highlights Purtscher's retinopathy and renal cortical necrosis might be considered as a recognized pair complication of acute pancreatitis.

Renal Cortical Necrosis in Postpartum Hemorrhage: A Case Series.

BACKGROUND: Pregnancy-related renal cortical necrosis may lead to end-stage renal disease. Although this obstetric complication had virtually disappeared in high-income countries, we have noted new cases in France over the past few years, all following postpartum hemorrhage. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 18 patients from 5 French nephrology departments who developed renal cortical necrosis following postpartum hemorrhage in 2009 to 2013. OUTCOMES: Obstetric and renal features, therapeutic measures, and kidney disease outcome were studied. RESULTS: All patients had a severe postpartum hemorrhage (mean blood loss, 2.6±1.1 [SD] L). Hemodynamic instability and disseminated intravascular coagulation were reported in 5 and 11 patients, respectively. All developed rapid onset of acute kidney injury and required hemodialysis. Diagnosis of renal cortical necrosis was performed 4 to 33 days following delivery. At 6 months postpartum, 8 patients remained dialysis dependent and none recovered normal kidney function. The length of exposure to tranexamic acid treatment was significantly more prolonged in women whose estimated glomerular filtration rate remained <15mL/min/1.73m(2) (7.1±4.8 vs 2.9±2.4 hours; P=0.03). LIMITATIONS: Retrospective study; small sample size. CONCLUSIONS: In the setting of gravid endothelium, the conjunction of disseminated intravascular coagulation with the life-saving use of procoagulant and antifibrinolytic agents (recently implemented in France in a postpartum hemorrhage treatment algorithm) may give rise to a risk for uncontrolled clotting in the renal cortex and hence irreversible partial or diffuse cortical necrosis.

Human kidney damage in fatal dengue hemorrhagic fever results of glomeruli injury mainly induced by IL17.

Acute kidney injury is an unusual complication during dengue infection. The objective of this study was to better identify the characteristics of glomerular changes focusing on in situ immune cells and cytokines. An immunohistochemical assay was performed on 20 kidney specimens from fatal human cases of dengue hemorrhagic fever (DHF). It was observed a lymphomononuclear infiltrate, neutrophils and nuclear fragmentation in the glomeruli, hydropic degeneration, nuclear retraction, eosinophilic tubules and intense acute congestion. Sickle erythrocytes were frequent in glomeruli and inflammatory infiltrate. The glomeruli presented endothelial swelling and mesangial proliferation. Lymphocytes CD4+ predominated over CD8+ T cells, B cells and natural killer cells. There were also an expressive number of macrophagic CD68+ cells. S100, Foxp3 and CD123 cells were not identified. Cells expressing IL17 and IL18+ cytokines predominated in the renal tissues, while IL4, IL6, IL10, IL13, TNF-alpha and IFN-gamma were rarely visualized. The high number of cells expressing IL17 and IL18+ could reflect the acute inflammatory response and possibly contribute to the local lesion. CD8+ T cells could play a role in the cytotoxic response. DHF is a multifactorial disease of capillary leakage associated with a "Tsunami of cytokines expression". The large numbers of cells expressing IL17 seems to play a role favoring the increased permeability.