Tubular Necrosis Research Articles

Element analysis applied to investigate acute kidney injury induced by red yeast rice supplement.

Silica nanoparticles are used in functional foods and tablets to increase drug stability and delivery. We investigated a patient with acute kidney injury with Fanconi syndrome after taking functional food tablets made from red yeast rice using low-vacuum scanning electron microscopy (LVSEM) with an element analysis system. Kidney biopsy revealed proximal tubular necrosis and vacuolization with 10-20nm black granules, which were similar to the silica nanoparticles found in the functional food tablets and urinary samples, as determined via LVSEM with element analysis. Reabsorbed silica nanoparticles induce oxidative stress in the kidney. Element analysis by LVSEM is useful to investigate a possible cause of acute tubular necrosis in patients with Fanconi syndrome.

Mesenchymal stem cell-derived exosomes in renal ischemia-reperfusion injury: a new therapeutic strategy.

Renal ischemia-reperfusion injury (RIRI) is a serious kidney condition that causes significant damage due to lack of blood flow. This injury leads to oxidative stress and inflammation, which can cause acute tubular necrosis and kidney failure. Stem cell-derived exosomes, small vesicles released by stem cells, have shown promise in treating RIRI. Mesenchymal stem cells (MSCs) have been used to mitigate RIRI, and their exosomes have been found to play a crucial role in repairing damaged tissues. This review explores the key roles of exosomes from different sources of MSCs in RIRI, the potential of MSC-derived exosomes in treating this disease, and future research directions.

Association of Oral Tobacco-Free Nicotine Delivery Product with Acute Renal Tubular Necrosis

Usage of novel non-tobacco oral nicotine delivery products (ONDPs) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco-containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. A 19-year-old male transplant recipient presented with flank pain and a few days’ history of intake of ZYNR pouches. Immunosuppression was with tacrolimus, mycophenolate, and steroids. Baseline serum creatinine was 1.1–1.3 mg/dL. Laboratory evaluation showed elevated C-reactive protein, increased serum creatinine and blood urea nitrogen, leukocytosis, neutrophilia, and increased lactate dehydrogenase (LDH). Infectious disease work-up was negative. A kidney transplant biopsy showed severe acute tubular injury/necrosis (ATN) without evidence of rejection. Donor-specific antibodies were negative. Other etiologies of hemolysis were negative. He did not require renal replacement therapy. Kidney function and LDH improved gradually. The most recent follow-up eight months after presentation showed a serum creatinine level of 2.6 mg/dL with stable electrolytes, with eGFR of 35 mL/min/1.73 m2. Here, we describe a 19-year-old adolescent with a kidney transplant who sustained ATN leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study ATN as a possible renal manifestation of these next-generation products to raise awareness among the public.

A Case Report of a Suspected Neonatal Alloimmune Thrombocytopenia in a Tertiary Health Institution

Fetal and neonatal alloimmune thrombocytopenia FNAIT is the leading cause of severe thrombocytopenia in the fetus and neonate leading to serious bleeding, intracranial haemorrhage and death and also intracranial haemorrhage in full-term infants. We reported a case of a 33-year-old woman who was delivered of a male neonate via Emergency lower segment Cesarean section CS on account of premature rupture of the membrane with oligo hydramnios at an estimated gestational age EGA of 29 weeks 3 days. Her blood group is O Rhesus D positive, and Genotype HbAA. No known premorbid illness. Her last confinement was of a male child delivered via CS and died within 12 hours of birth. This reported case of suspected FNAIT was a baby received alive after CS with birthweight of 1,060g and APGAR score of 7185 transiently, and was noticed to be bleeding from the mouth and anus shortly after birth. Thereafter, he had thrombocytopenia, persistent anaemia, several apneic attacks, seizures, desaturation and died after 42 hours of life despite all prompt clinical interventions. Autopsy summary includes anaemia, central cyanosis, petechial hemorrhage, diffuse alveolar damage, cerebral edema, acute tubular necrosis, small for gestational age and placental vasculopathy. Conclusion: Fetal and neonatal alloimmune thrombocytopenia is a rare disorder and yet poses a challenging diagnosis and treatment plan in resource-limited centres especially in developing countries. Although the clinical findings of the reported suspected case were not classical as previously reported by other studies, they’re pointers to our curiosity and open to further criticism.

What is the spectrum of kidney pathology associated with COVID-19?

Kidney involvement occurs in almost one third of patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with increased disease severity. This review aims to outline the spectrum of kidney pathology involved in COVID-19. Literature was reviewed systematically on the databases Medline OVID and Scopus in search of case reports, case series, cohort studies and autopsy studies of patients with COVID-19 who underwent kidney biopsies. Studies were published between August 2020 and November 2021. Fourteen studies consisting of 159 patients were included in this review. Acute tubular necrosis is the most common pathology followed by collapsing glomerulopathy, occurring in 40.1% and 28.9% of patients respectively. Of the 46 patients with collapsing glomerulopathy, 44 were of African descent with high-risk apolipoprotein L1 genotypes. Less common glomerular diseases include membranous nephropathy, secondary focal segmental glomerulosclerosis, minimal change disease and primary focal segmental glomerulosclerosis occurring in 5%, 4.4%, 3.1% and 2.5% of patients respectively. Glomerulonephritis occurred in a minority of patients. Direct viral infection has not been found as a definitive aetiology. Acute kidney injury occurs frequently in hospitalised COVID-19 patients and is associated with increased morbidity and mortality. The mechanisms underpinning acute kidney injury are multifactorial. Acute tubular necrosis is the most common. Collapsing glomerulopathy is the most common glomerular injury and is strongly linked to apolipoprotein L1 genotypes. Improved understanding of COVID-19-related kidney pathologies can guide treatment to improve patient outcomes and reduce progression of chronic kidney disease. The longitudinal impact of COVID-19-related kidney disease requires further research.

Effect of Arabic Gum on Gentamicin Nephrotoxicity in Mice: A Pathological Study

<p><strong>Aim</strong> To investigate the effect of Arabic gum on gentamycin nephrotoxicity in mice kidney.<br /><strong>Methods</strong> Forty (40) mice were divided into five groups, eight mice in each. Group one (G1) stands for the negative control group. The second one (G2) was injected with gentamycin only, while the third one (G3) was given an Arabic gum orally 10g/kg. The 4th group (G4) was injected with gentamycin for 8 days, and then followed by Arabic gum orally for 8 days. The fifth group (G5) was injected with gentamycin plus oral administration of Arabic gum at the same time. A scoring system (+1-+4) was used to grade the histological features in the kidneys.<br /><strong>Results</strong> The results revealed a significant increase in body weight in G3 group only; this group presented a significant decrease in the level of both urea and creatinine. Group G2 showed a marked elevation in both serum urea and creatinine. Acute tubular necrosis (+4), in both G2 and G5. In G3, kidney sections presented mild cell swelling of the tubular epithelium in addition to the normal architectures (score +1), while G4 sections revealed tubular hyalin cast, expansion of glomerular tufts.<br /><strong>Conclusion</strong> The research indicates that gentamycin leads to kidney damage in mice. Arabic gum could be a treatment option although additional studies are required to determine the best dosing and timing, for optimal effectiveness.</p>

Proteinuria and proximal tubular epithelial cells: correlation between immunofluorescence, histology, and degree of proteinuria.

Proteins are filtered from the blood through the glomerular filtration barrier. Filtered proteins are reabsorbed by proximal tubular epithelial cells (PTECs), which have been shown to possess the ability to regulate protein reabsorption. Histologically, these reabsorbed proteins are seen as tubular protein reabsorption droplets (TPRDs). Experimental studies indicate that PTECs play an important role in regulating proteinuria but the correlations between TPRD and the degree of proteinuria in human kidney biopsies have not been investigated in detail. Consecutive native kidney biopsies with non-proliferative glomerular disease performed at the OSUWMC for a 1-year period were analyzed. Cases with acute glomerular diseases and inadequate biopsies were excluded. The staining intensity and the percentage of TPRDs, as well as other morphologic parameters, were assessed. A total of 109 kidney biopsies were included in the study. A reverse correlation was identified between the percentage of albumin TPRDs and proteinuria (p = 0.047). There were positive correlations between proteinuria and the staining intensity for IgG TPRDs (p = 0.05) and the degree of acute tubular necrosis (ATN) (p = 0.015). In patients with no ATN, positive correlations between proteinuria and albumin and IgG TPRDs were seen, whereas in patients with ATN, these correlations were lost. A positive correlation was seen between proteinuria and chronic kidney injury. A strong correlation was noted between the degree of proteinuria and podocyte foot process effacement. Our data indicate that PTECs regulate proteinuria by absorbing proteins from the urine filtrate. Therefore, based on the human renal biopsy material, our study confirms that well-functioning renal PTECs play an important role in the regulation of proteinuria.

Drug-induced acute kidney injury: a cohort study on incidence, identification of pathophysiological mechanisms, and prognostic factors.

Acute Kidney Injury (AKI) is a common clinical syndrome characterized by an abrupt decline in the glomerular filtration rate (GFR), which can cause severe alterations in blood volume and acid-base balance. Drug-Induced Acute Kidney Injury (DI-AKI) is associated with exposure to nephrotoxic medications, particularly among hospitalized patients. Adverse drug reactions comprises type A and type B reactions. Type A reactions are predictable based on the pharmacology of the substance, dose-dependent, and manifest as Acute Tubular Necrosis (ATN). Type B reactions are unpredictable, idiosyncratic, not dose-dependent, and manifest as Acute Interstitial Nephritis (AIN), Crystal-Induced Nephropathy, among others. To evaluate DI-AKI incidence, identify the main associated drugs and the pathophysiological mechanism of the observed injury, analyze prognostic factors associated with unfavorable outcomes, and compare the outcomes of death and the need for Acute Kidney Support Therapy (AKST) between patients with DI-AKI vs. AKI due to other etiologies. A retrospective cohort study conducted at the Hospital das Clínicas of the Faculty of Medicine of Botucatu - UNESP (HC-FMB), using data from patients hospitalized between January 2016 and April 2022 and followed, via consultation, by the AKI-Nephrology team. Inclusion criteria: diagnosis of AKI and Chronic Kidney Disease (CKD) with superimposed AKI. Exclusion criteria: patients under 18 years old or on chronic Renal Replacement Therapy. AKI was diagnosed based on creatinine increase as established by KDIGO 2012. Data were presented as mean and standard deviation or median with interquartile range and frequency. Statistical significance was set at 5% (p < 0.05). Comparative analyses were performed using the Chi-Square test for categorical variables and the T-test for continuous variables. Subsequently, logistic regression was performed to identify factors associated with the need for AKST and death. A total of 1,398 patients were analyzed, most of them males (61.4%), with a mean age of 64 years ±14.4 years. The most prevalent etiology of AKI was Mixed Ischemic + Septic AKI (28%). DI-AKI was a significant cause of AKI (19.3%). Of these, 25.2% were isolated DI-AKI and 74.8% were Mixed DI-AKI + Ischemia and/or Sepsis. Among patients with DI-AKI, the mean age was 61.15 ± 15.26, males were the most frequent, the majority were not subjected to AKST and survived. Most of these patients were hospitalized in the ward, did not need vasoactive drugs, nor did they use mechanical ventilation. DI-AKI showed lower severity and mortality compared to other AKI etiologies but had a similar need for AKST (26.3% vs. 35.4%, p < 0.05 and 31.8% vs. 36.8%, p > 0.05). Most nephrotoxic drugs caused type A reactions, with Vancomycin being the primary nephrotoxin. Among drugs associated with DI-AKI, Vancomycin was associated with a higher need for AKST and death, while Amphotericin B was associated with a lower risk of AKST and death. Although the mortality rate is lower among DI-AKIs compared to other AKI etiologies, the need for AKST was similar. Therefore, it is recommended that DI-AKI be recognized early to enable dose reduction or even drug suspension, depending on the type of reaction, to reduce healthcare costs and improve clinical outcomes for patients.

Outcomes of acute kidney injury continuum in children.

Acute kidney injury (AKI) is associated with high morbidity and mortality. The continuum of kidney damage after an AKI episode is poorly explored in the paediatric population. We performed a retrospective cohort study on 2346 children with AKI from a tertiary care hospital in Romania over a 9-year period. The main objective was to evaluate the impact of AKI duration on mortality and the risk of new-onset chronic kidney disease (CKD). Out of 2346 AKI patients, transient AKI was present in 655 patients (27.9%), persistent AKI in 1009 children (43%) and acute kidney disease in 682 patients (29.1%). In contrast to transient AKI, children who developed acute kidney disease were younger, with a higher degree of anaemia, lower number of platelets, higher procalcitonin, higher LDH, higher GGT, higher urea and higher serum creatinine levels. The pre-renal cause of AKI was the leading cause regardless of AKI duration. As kidney injury progressed over time, there was an increasing incidence of the intrinsic causes of AKI (11.1% in transient AKI, 13.2% in persistent AKI and 22.6% in acute kidney disease). Acute kidney disease patients had the highest mortality rate (16.42%), followed by transient AKI (14.66%) and persistent AKI (9.81%). Overall mortality increased in the presence of renal microvascular alterations, acute tubular necrosis, lower haemoglobin, serum proteins and platelets, and higher procalcitonin levels. The continuum of AKI expressed as acute kidney disease resulted in an increased risk of new-onset CKD. CKD was influenced by the intrinsic cause of AKI and not by AKI severity.

A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi.

The study aimed to verify the pathogenic malarial kidney infections and histopathological pictures in mice infected with Plasmodium chabaudi using Indigofera oblongifolia leaf extract silver nanoparticles (IOLEAgNPs). Fifty healthy adult female mice C57BL/6 were used. Animals were divided into five groups, with each group of ten mice. The first control non-infected group was given distilled water for 7 days. The second group was orally given 50 mg/kg of IOLEAgNPs. The third, fourth, and fifth groups were injected intraperitoneally with 105 parasitized erythrocytes of P. chabaudi. After 1 h, the fourth group received 50 mg/kg of IOLEAgNPs, while the fifth group orally received 10 mg/kg chloroquine phosphate. The histopathology of the kidney was studied by routine histology method with hematoxylin-eosin staining. The kidney revealed cerebral microvessel congestion, hemorrhages, and necrosis. Cast formation, glomerulonephritis, tubular necrosis, and congestion were observed in the kidney cortex. Consequently, the targeted medical IOLEAgNPs reduced this degeneration impact on renal tissue. Proven that plant-source synthesized IOLEAgNPs play a preventive role as antimalarial agents in female mice infected with P. chabaudi.

Role of Vitamin C on methotrexate-induced nephrotoxicity in psoriasis context: A preclinical assessment

Methotrexate (MTX) is the most prescribed drug for systemic treatment of psoriasis. However, its clinical use is limited by its nephrotoxicity, which antioxidants can attenuate. This study evaluates the impact of vitamin C (vitC), a well-known antioxidant, on nephrotoxicity induced by high MTX doses in the context of psoriasis. To achieve this purpose, the kidney injury triggered by acute MTX exposure was established in an imiquimod-induced psoriasis-like mouse model. Mice were randomly divided into six groups: group 1 (control); group 2 (Imiquimod, IMQ), group 3 (IMQ+vitC 175 mg/kg/day); group 4 (MTX 20 mg/kg i.p); group 5 (IMQ+MTX 20 mg/kg) and group 6 (IMQ+MTX 20 mg/kg + vitC 175 mg/kg/day). The effects of these treatments were determined by considering the evolution of IMQ-induced skin lesions and serum creatinine levels. Moreover, histopathological analysis, lipid peroxidation, oxidative stress, and TNF-α production were determined in kidney tissue. Results showed that vitC attenuates renal damage in the context of IMQ-induced psoriasis. However, the opposite occurs when administered with IMQ+MTX, worsening skin psoriasis lesions and exacerbating acute renal tubular necrosis and oxidative DNA damage. These results establish new clues about the MTX-induced nephrotoxicity in the psoriasis context and the putative protective effects of vitC. It suggests that vitC supplementation could help attenuate the renal damage promoted by the psoriatic pathological environment. However, it should be avoided in psoriasis patients with renal dysfunction treated with MTX.

Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients.

Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If kidney histology is an essential key, the anatomopathological data remain weak although essential to this complex management. Patients with active cancer who had a kidney biopsy (KB) between 2014 and 2020 were included, and their clinicobiological and histological data were analyzed retrospectively. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years. One hundred twelve patients presented with proteinuria, 95 with acute kidney injury, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of KBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a pre-renal (15 patients) and kidney disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses reflecting the complexity of kidney damage in cancer. Different clusters were found, highlighting that immunotherapy and anti-VEGF were the most commonly involved drugs. During onconephrology practice, kidney toxicity of treatments is the most common etiology. Several mechanisms can be involved, underscoring the importance of kidney biopsy and the complexity of its management. Chronic histological lesions were very common.

Effect of alpha-linolenic acid on aminoglycoside nephrotoxicity and RhoA/Rho-kinase pathway in kidney.

Aminoglycoside nephrotoxicity stands as a primary contributor to the development of acute intrinsic renal failure. Distinctive characteristic associated with this nephrotoxicity is the occurrence of tubular necrosis, which is why it is commonly referred to as acute tubular necrosis. Studies have demonstrated that inhibiting rhoA/rho-kinase pathway is beneficial for kidney damage induced by diabetes and renal ischemia. Comparable pathological conditions can be observed in aminoglycoside nephrotoxicity, like those found in diabetes and renal ischemia. Gentamicin, an aminoglycoside, is known to activate Rho/Rho-kinase pathway. The primary goal of this study is to explore influence of oxidative stress on this pathway by concurrently administering gentamicin and alpha-linolenic acid (ALA) possessing known antioxidant properties. To achieve this, gentamicin (100 mg kg-1) and ALA (70 mg kg-1) were administered to mice for a period of 9 days, and Rho/Rho-kinase pathway was examined by using ELISA. Administration of gentamicin to mice led to an elevation in RhoA and rho-kinase II levels, along with the activity of rho-kinase in kidneys. However, ALA effectively reversed this heightened response. ALA, known for its antioxidant properties, inhibited activation of Rho/Rho-kinase pathway induced by gentamicin. This finding suggests that gentamicin induces nephrotoxicity through oxidative stress.

Renal protective potential of pentoxifylline, chlorpromazine, and lovastatin in ischemia-reperfusion injury: An experimental study.

This study aimed to evaluate the ability of pentoxifylline when compared to lovastatin and chlorpromazine as nephroprotective substances in cases of renal ischemia and reperfusion syndrome (IRI). A total of 36 adult male animals were randomly allocated into four groups (untreated control group, pentoxifylline group, lovastatin group, and chlorpromazine group), each consisting of nine animals. All groups were submitted to experimental ischemia and reperfusion procedures. The animals were evaluated 24, 72 and 120 hours after IRI, including physical examinations, serum urea and creatinine measurements, as well as histopathological, morphometric, and stereological analyses of the renal tissue. Results indicated that 24 hours after IRI, only chlorpromazine was effective in controlling azotemia. At the 72-hour mark, both chlorpromazine and pentoxifylline exhibited efficacy. After 120 hours, all three substances demonstrated renal protective qualities. Pentoxifylline was the most effective in preserving the structural integrity of kidney tissue, followed by chlorpromazine. In conclusion, all three treatments (pentoxifylline, chlorpromazine, and lovastatin) were effective. Pentoxifylline proved to be promising in the response against acute tubular necrosis, although chlorpromazine presented earlier renoprotective effects in terms of maintaining renal function.

Tyrosine Kinase Inhibitor Induced Proteinuria - A Review.

Tyrosine Kinase inhibitor (TKI) is a class of drugs that interfere with protein kinases' signal transduction pathways through an array of inhibitory mechanisms. Tyrosine kinases (TK) have an inevitable role in downstream signal transduction and the proliferation of tumour cells. Hence, tyrosine kinase inhibitors (TKIs) are frequently employed as anti-neoplastic agents in the treatment of colon, breast, kidney, and lung cancers. They can be used as single or combination therapy with other targeted therapies. It is understood that TKIs pose a risk of developing proteinuria in some patients as it can primarily result in dysfunction of the split diaphragm, constriction or blockage of capillary lumens mediated by the basement membrane, acute interstitial nephritis, or acute tubular necrosis. This paper reviews the mechanism of action of TKIs, the pathophysiological mechanism of TKI-induced proteinuria, and its management Fig. 1.

Histopathological changes in the human tissues in various types of poisoning: A cross-sectional autopsy study

BackgroundPoisoning is a critical health issue caused by exposure to harmful substances, leading to a range of biological effects from mild irritation to severe organ damage and death. Acute poisoning is particularly prevalent in developing countries reliant on agriculture, where agricultural poisons such as organophosphates, carbamates, pyrethroids, and aluminum/zinc phosphide are common. This study aims to analyze the histopathological changes in various organs in autopsy of poisoning cases to understand the extent and nature of organ damage. MethodsAutopsies were performed on cases with an established or suspected history of poison ingestion. Tissue samples from the stomach, intestine, liver, spleen, kidneys, brain, and lungs were examined for histopathological changes. ResultsOut of 52 cases analyzed, aluminum phosphide was the predominant poison, accounting for 76.92 % of cases. Histopathological findings in poisoning cases included significant pulmonary edema (55.77 %), intra-alveolar hemorrhage (48.08 %), liver ballooning degeneration (48.08 %), acute tubular necrosis (51.92 %) in kidney, and universal brain and spleen congestion (100 %). Stomach findings showed partial loss of rugosity (80.77 %), congestion (51.92 %), necrosis of the mucosa (30.77 %), congestion (71.15 %), denudation of the epithelium (48.08 %), and mucosal inflammation (48.08 %) as predominant findings. Aluminum phosphide caused severe histopathological changes across all examined organs. ConclusionThe study highlights the critical role of histopathological examination in diagnosing and understanding organ damage in poisoning cases. Forensic pathologists can use these histopathological patterns as reference points to differentiate poisoning from other causes of death, aiding in accurate diagnosis and targeted treatment.

Histopathologic and ultrastructural findings in oak (Quercus spp.) toxicity on 2 beef cattle farms in Colorado.

Natural oak toxicity, a phenomenon sporadically reported in the United States, is due to consumption of any part of most oak trees (Quercus spp.). Ruminants, mainly cattle, are disproportionately susceptible to oak toxicity. Toxicity is attributed to degradation of the oak plant hydrolysable tannins by rumen microbes and enzymes into absorbable low-molecular-weight metabolites, which are postulated to bind and damage endothelial cells by unknown mechanisms. The clinical manifestations of acute toxicosis are nonspecific or broadly suggestive of renal disease due to acute tubular injury. Here we document the clinical, gross, histopathologic, and novel ultrastructural features of natural acute oak nephrotoxicity in 3 beef calves on 2 farms in Colorado, USA. Gross postmortem findings included perirenal edema with renomegaly and hemorrhagic gastroenteritis. Histologically, renal tubular epithelial necrosis was severe, with hemorrhage and intratubular hyaline casts. Transmission electron microscopy revealed extensive involvement of proximal and distal convoluted tubules, with predominantly intact basement membranes, and glomerular and interstitial endothelial injury and necrosis. The ultrastructural details of toxic nephropathy and vasculopathy induced by oak metabolites in natural cases of bovine oak toxicosis have not been described previously, to our knowledge.

Clinical correlates and pathology of non-diabetic renal disease in diabetes mellitus

Objectives: Early identification and differentiation of patients with non-diabetic renal disease (NDRD) from diabetic nephropathy (DN) or those with NDRD superimposed on DN improves the prognosis and reduces associated morbidity. The objectives of the study were to compare the clinical profile, nature of renal involvement, and etiopathogenesis (renal biopsy) of patients with isolated NDRD and NDRD superimposed on DN. Materials and Methods: It is a descriptive study in patients with T2D and renal involvement suggestive of non-diabetic etiology further evaluated with renal biopsy and grouped as NDRD alone or NDRD with DN. Results: Of the total 50, 66% were male, the mean age was 55.57 ± 12.28 years, and all were proteinuric. Overall, isolated NDRD and NDRD superimposed on DN were observed in 64% and 36% of patients, respectively. Diabetic retinopathy was absent in 82% of cases. The most common finding in isolated NDRD was membranous nephropathy, followed by immunoglobulin A (IgA) nephropathy and rapid progression of glomerular nephritis (RPGN). At the same time, in the NDRD and DN group, maximum patients displayed IgA nephropathy followed by acute tubular necrosis and RPGN. The incidence of atypical features of renal disease was almost twice as high in the isolated NDRD group than in the group with both NDRD + DN. Conclusion: NDRDs are highly prevalent, and DN may superimpose these. Recognizing NDRD solely on the basis of clinical indicators is challenging. Therefore, histopathological analysis seems essential to accurately diagnose NDRD in diabetic patients to reduce the probability of missed NDRD diagnosis and initiate prompt treatment.

6695 When Pheochromocytoma Presents As Acute Renal Failure, With Complete Resolution, A Case Report

Abstract Disclosure: U.A. Siddiqui: None. D. Deyar: None. D. Bondarenko: None. M. Ahmad: None. K.K. Lessard: None. Pheochromocytomas and paragangliomas (PPGL), are rare neuroendocrine tumors (0.66/ 100,000 cases), often characterized by paroxysmal hypertension and associated symptoms. While cardiac complications have been well-documented in the literature, there is limited information regarding acute renal failure. We explore a unique case of pheochromocytoma presenting initially with hypertensive crisis, but also with an unexpected journey into acute renal failure and subsequent recovery. 62-year-old hispanic male without known past medical history presents to the emergency department with chest pain, epigastric pain, dyspnea, and emesis. He was tachypneic, febrile (101°F), hypoxic (83% on room air), and profoundly hypertensive (188/112 mmHg). CT scan showed pneumonia as well as a 7cm complex mass within the left adrenal gland. Admitting labs showed metabolic acidosis, acute kidney injury (Cr 2.52mg/dL) and elevated troponins. Echocardiogram showed a reduced ejection fraction 45-50% and coronary angiography showed mild nonocclusive coronary artery disease. MRI visualized a solid left adrenal mass measuring 6.8cm with enhanced, mixed T1/T2 signaling and drop out inconsistent with adenoma. Adrenal labs revealed ACTH 125 pg/mL (9-46 pg/mL) and cortisol 27mcg/dL free metanephrine (MN) 1,422 pg/mL (&amp;lt;57 pg/mL), and free normetanephrine (NMN) &amp;gt;20,000 pg/mL (&amp;lt;148 pg/mL), total free MN + NMN &amp;gt;40,000 pg/mL (&amp;lt;205 pg/mL). Preoperative MIBG scan showed increased tracer activity of the left adrenal consistent with pheochromocytoma. Alpha blockade was performed using doxazosin and carvedilol was continued. Unfortunately, he developed oliguria and rising creatinine ( 7.4mg/DL). Kidney biopsy showed findings of acute tubular necrosis and mild fibrosis. Hemodialysis was initiated, receiving 12 sessions prior to undergoing open left adrenalectomy with mass resection on day 22 of admission. Post-operative blood pressure was managed with volume re-expansion and tapering of alpha blocker. Within 72 hours, renal function fully recovered and dialysis was discontinued. Follow up metanephrines are within normal limits and genetic testing results remain pending. Cases of acute renal failure and PPGL are scarce, and this case report contributes to the topic. Mortality in p is usually due to cardiovascular complications such as stroke, cardiomyopathy, and dysrhythmia [2]. Renal complications result from hypertensive nephrosclerosis or nephrotic syndrome. To date, only one case report from 1961 exists on acute tubular necrosis and PPGL [3]. We present an interesting case of pheochromocytoma complicated by hypertensive crisis and acute renal failure requiring dialysis. Resection of the pheochromocytoma normalized renal function. This demonstrates the importance of timely resection of the tumor and meticulous blood pressure management to ensure optimal outcomes. Presentation: 6/2/2024

8089 Myxedema Coma Presenting with Reversible Cardiomyopathy and Acute Renal Failure

Abstract Disclosure: A. Mubashir: None. F. Sajid: None. M. Sattar: None. Myxedema Coma is a life-threatening complication of hypothyroidism and often presents with multi-organ failure. However, reversible cardiomyopathy and acute renal failure are rare. Here, we present a case of iatrogenic hypothyroidism leading to myxedema coma with reversible organ failure. Case Presentation: A 58-year-old male with a past medical history of iatrogenic hypothyroidism after total thyroidectomy for follicular thyroid cancer, noncompliant with levothyroxine for the past three years, was brought to the hospital due to worsening mental status, low energy, and cold extremities for three days. On admission, vital signs were within normal limits. Laboratory studies revealed Random Glucose 113 (74-200 mg/dl), Na 134 (135-149 mmol/l), TSH: 217 (0.39-4.08 MCIU/ml), Free T4 &amp;lt;0.25 (0.58-1.64 ng/dl), Free T3 1.01 (2.53-3.87 pg/ml), BUN 53.3 (7-21 mg/dl), Creatinine 4.9 (0.5-1.3mg/dl). Urinalysis was positive for protein of 300 mg/dl (negative). Urine studies showed hematuria, total protein/cr 3.18 (&amp;lt;0.10), with increased total protein of 60/24 hours (0-12 mg/dl), suggesting glomerular etiology. Additionally, Bence Jones protein and monoclonal band were negative, interpreted as mild glomerular proteinuria. FeNa &amp;gt;2%, Urine sodium of &amp;gt;40 (20-40mmol/l) suggest acute tubular necrosis. EKG showed normal sinus rhythm with low voltage. To rule out diastolic dysfunction, an echocardiogram was performed, which revealed depressed systolic function with an ejection fraction of 31-35% and a large pericardial effusion with echocardiographic features of tamponade. He also had global cardiomyopathy with akinesis, especially in the inferior segments. He was treated with IV levothyroxine. Repeat imaging in one month showed an increase in ejection fraction to 55% with moderate-sized pericardial effusion and no echocardiographic features of tamponade. Global cardiomyopathy had also resolved. However, left ventricular systolic function was borderline, with delayed diastolic expansion of the right ventricle. Repeat creatinine was 2mg/dl. The patient’s condition greatly improved, and he was discharged with follow-up with endocrinology, nephrology, and cardiology. Discussion: In the available literature, diastolic dysfunction is associated with severe hypothyroidism. However, reversible global cardiomyopathy with decreased systolic function is rare. The pathogenesis of this myopathy is not well understood. Similarly, known mechanisms of renal injury in hypothyroidism include renal hypoperfusion, rhabdomyolysis, decreased kidney-to-body weight ratio, truncated tubular mass, and altered glomerular architecture. While the need to perform a renal biopsy or the use of goal-directed therapy for dilated cardiomyopathy remains questionable in such cases, reversible complications of severe hypothyroidism should be investigated in patients with suspected myxedema. Presentation: 6/2/2024