A Rare Case of Severe Preeclampsia and HELLP (Hemolysis, Increased Liver Enzymes, Low Platelets) Syndrome With Complex Clinical Presentation.

Severe preeclampsia is a disorder of pregnancy, characterized by increased blood pressure (>140/90 mmHg) and proteinuria (≥ 300 mg/24 hours) at later than 20 weeks of gestation. Particularly in underdeveloped nations, severe preeclampsia and eclampsia have a significant negative impact on the health of expectant mothers, fetuses, and newborns. The HELLP (hemolysis, increased liver enzymes, low platelets) syndrome is thought to be a subset of preeclampsia, a group of hypertensive disorders of pregnancy that also includes eclampsia. Compared to preeclampsia alone, maternal and fetal problems are more severe in HELLP. There can be a diagnostic dilemma that arises when attempting to differentiate HELLP from its numerous imitators to determine the appropriate course of treatment. Here, we present a rare case of a pregnant woman presenting with preeclampsia complicated by manifestations and investigations suggestive of HELLP syndrome with acute kidney injury (AKI), retinal detachment, and symptoms of DIC (disseminated intravascular coagulation), which can be grievous to the mother as well as the fetus.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats.

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury. However, the standard diagnosis based on plasma creatinine as well as novel injury biomarkers lacks enough pathophysiological specificity. Further granularity in the detection of renal injury would help understand the implications of individual damage patterns needed for personalized patient handling. In this article, we studied the association of urinary ganglioside GM2 activator protein (GM2AP) with the patterns of tubular damage produced by 5 and 10 mg/kg cisplatin in rats. Our results show that GM2AP appears in the urine only following damage to the cortical segment of the proximal tubule. The information provided by GM2AP is not redundant with but distinct and complementary to that provided by urinary neutrophil gelatinase-associated lipocalin (NGAL). Similarly, treatment with 150 mg/kg/day gentamicin damages the renal cortex and increases GM2AP urinary excretion; whereas renal ischemia, which does not affect the cortex, has no effect on GM2AP. Because of the key role of the cortical proximal tubule in renal function, we contend GM2AP as a potential diagnostic biomarker to stratify AKI patients according to the underlying damage and follow their evolution and prognosis. Prospectively, urinary GM2AP may help grade the severity of platinated antineoplastic nephrotoxicity by forming part of a non-invasive liquid biopsy.

Histopathological and Immunohistochemical Study of Acute Tubular Injury in Native Kidney Biopsy.

Background: Acute tubular injury (ATI) is a common diagnosis on renal biopsy. There are no accepted parameters to assess the severity of injury or predict recovery. An objective histologic grading system would be of immense value in clinical practice. The macrophage response to injury involves the MI phenotype which is proinflammatory and M2 which is prorepair. The study of these macrophages could aid in studying the severity and the recovery. Materials and Methods: A total of 58 native kidney biopsies with features of ATI and a minimum follow-up of 12 weeks were graded into mild, moderate and severe, using scores for simplification, sloughing, and mitosis. These scores and the density of macrophages stained with CD68, CD163, and HLA-DR were correlated with serum creatinine at presentation and with recovery. The effect of chronicity index as measured by glomerulosclerosis, tubular atrophy, and interstitial fibrosis and of co-morbidities of age, hypertension, and diabetes on the recovery pattern was also studied. Results: All three histologic scores and the grades of ATI showed positive correlation with the serum creatinine level. The densities of CD 68 + and CD163 + macrophages also showed a significant correlation with serum creatinine level. However, none of these these histological features nor the macrophage densities predicted clinical recovery. Age >60 years, hypertension, diabetes, and chronicity score on biopsy were indicators of partial and delayed recovery. Conclusion: The histopathological semiquantitative scoring system can be used routinely to grade ATI. However none of the studied parameters predicted recovery.

Multiorgan Dysfunction in a Patient With Adult-Onset Still's Disease Flare: A Case Report.

Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder. A 71-year-old lady who was on treatment for AOSD presented with clinical evidence of heart failure and was subsequently found to have impaired renal and hepatic function. Following extensive workup including a liver biopsy, the cause of liver dysfunction was determined to be congestive hepatopathy, while renal dysfunction was presumed to stem from the low output state. The etiology of myocardial dysfunction, driving liver and kidney injury, was considered to be myocarditis from AOSD or global myocardial dysfunction from a systemic inflammatory state. Management involved pulse-dose glucocorticoids followed by taper and anakinra for AOSD, alongside goal-directed medical therapy for cardiac failure. At follow-up after a month, hepatic and renal function had fully recovered, whereas cardiac function remained compromised, evidenced by persistently depressed ejection fraction and global hypokinesia on a repeat echocardiogram. This report delineates a systematic approach to multiorgan dysfunction in a patient with a rare condition such as AOSD and reviews the reported causes of hepatic and cardiac involvement in AOSD.

Pediatric early-phase anorexia nervosa without hypokalemia exhibiting acute tubular injury: a case report.

Anorexia nervosa can lead to kidney complications. Few studies reported kidney biopsy results in young adults, most of whom had chronic anorexia nervosa, and kidney biopsy findings in pediatric patients with early-phase anorexia nervosa are rarely reported. A 14-year-old girl who lost weight due to excessive exercise and reduced diet was admitted for kidney dysfunction. She was 147 cm tall and weighed 32.9 kg, with a body mass index of 15.2 kg/m2. She was 39 kg about a year earlier. Her heart rate and blood pressure were 30-40 beats/min and 108/68 mmHg, respectively. She had kidney dysfunction (estimated glomerular filtration rate, 56.6 mL/min/1.73 m2). Urine ß2-microglobulin was slightly elevated (393 µg/L), and percent tubular phosphate reabsorption was low (75.2%), suggesting tubular damage; however, hypokalemia was absent. Kidney dysfunction did not improve with fluid loading. Kidney biopsy revealed that all glomeruli were intact, with no vasculitis, interstitial inflammation or fibrosis on light microscopy. However, proximal tubular epithelial walls were flattened and the brush border was absent, suggesting acute tubular injury. Immunofluorescent staining was negative for immunoglobulins and complement proteins, and electron microscopy showed no significant electron-dense deposition. The patient's serum creatinine gradually declined, normalizing on the 17th day of admission. Unlike previous reports in young adults, kidney dysfunction was observed even in the absence of hypokalemia in the current pediatric patient with early-phase anorexia nervosa. Proximal tubular injury in early-phase anorexia nervosa may be caused by bradycardia without hypokalemia, leading to subsequent kidney dysfunction.

Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Adverse effects of acute tubular injury on the glomerulus: contributing factors and mechanisms.

The intricate relationship between tubular injury and glomerular dysfunction in kidney diseases has been a subject of extensive research. While the impact of glomerular injury on downstream tubules has been well-studied, the reverse influence of tubular injury on the glomerulus remains less explored. This paper provides a comprehensive review of recent advances in the field, focusing on key pathways and players implicated in the pathogenesis of tubular injury on glomerular dysfunction. Anatomical and physiological evidence supports the possibility of crosstalk from the tubule to the glomerulus, whereby various mechanisms contribute to glomerular injury following tubular injury. These mechanisms include tubular backleak, dysfunctional tubuloglomerular feedback, capillary rarefaction, atubular glomeruli, and the secretion of factors from damaged tubular epithelial cells. Clinical evidence further supports the association between even mild or recovered acute kidney injury and an increased risk of chronic kidney disease, including glomerular diseases. We also discuss potential therapeutic interventions aimed at mitigating acute tubular injury, thereby reducing the detrimental effects on glomerular function. By unraveling the complex interplay from tubular injury to glomerular dysfunction, we aim to provide insights that can enhance clinical management strategies and improve outcomes for patients with kidney disease.

An Interesting Case of Hypothyroidism Associated Acute Kidney Injury.

Muscle involvement is common in hypothyroidism. However, hypothyroidism as a causal factor for severe rhabdomyolysis and acute kidney injury (AKI) is rarely reported. We report a case of a 56-year-old Arab male who presented with unexplained acute worsening of chronic kidney disease. The patient was detected to have hypothyroidism and rhabdomyolysis on laboratory investigations. However, thyroxine replacement led to partial recovery of renal function. CPK also improved with vigorous hydration and thyroxine replacement. Although this is a rare association, in the absence of other causes of rhabdomyolysis, hypothyroidism should be suspected in patients presenting with AKI and high creatinine phospho-kinase.

Immunoglobulin G deposition on proximal tubules and the tubular basement membrane in acute tubular injury complicated with focal segmental glomerulosclerosis (FSGS): A possible prediction tool for subclinical FSGS.

Immunofluorescent deposition of immunoglobulin G (IgG) in the tubular basement membrane (TBM) has been evaluated in the diagnosis of various diseases; however, few studies have investigated the immunofluorescence of acute tubular injury (ATI). Herein, we attempted to clarify IgG expression in the proximal tubular epithelium and TBM in ATI due to various causes. Patients with ATI with nephrotic-range proteinuria, including focal segmental glomerulosclerosis (FSGS, n = 18) and minimal change nephrotic syndrome (MCNS, n = 8), ATI with ischemia (n = 6), and drug-induced ATI (n = 7), were enrolled. ATI was evaluated by light microscopy. CD15 and IgG double staining and IgG subclass staining were performed to evaluate immunoglobulin deposition in the proximal tubular epithelium and TBM. IgG deposition was identified in the proximal tubules only in the FSGS group. Furthermore, IgG deposition in the TBM was observed in the FSGS group showing severe ATI. IgG3 was predominantly deposited by the IgG subclass study. Our results indicate that IgG deposition in the proximal tubular epithelium and TBM suggests the leaking of IgG from the glomerular filtration barrier and its reabsorption by proximal tubules, which may predict disruption of the glomerular size barrier, including subclinical FSGS. FSGS with ATI should be included as a differential diagnosis when IgG deposition in TBM is observed.

Nivolumab-induced acute tubular injury: A case report.

Nivolumab belongs to immune checkpoint inhibitors (ICIs). ICIs-induced kidney injury is rare and acute interstitial nephritis (AIN) is the majority. A 58-year-old woman had gastric cancer treated with nivolumab. Her serum creatinine (Cr) increased to 5.94 mg/dL post 2 cycles of nivolumab and co-administered with acemetacin. A kidney biopsy showed acute tubular injury (ATI). Nivolumab rechallenge was done and Cr worsened again. The lymphocyte transformation test (LTT) indicated a strong positive for nivolumab. Although rare, ATI due to ICIs could not be ruled out, and LTT is a tool to identify the culprit.

Biopsy-proven first dose of oxaliplatin-induced acute tubular necrosis leading to end-stage renal failure: a case report.

BACKGROUND: Oxaliplatin is an anticancer therapy for pancreatic, gastric, and colorectal cancers. It is also used in patients with carcinomas of unknown primary sites. Oxaliplatin is associated with less frequent renal dysfunction than other conventional platinum-based drugs such as cisplatin. Albeit, there have been several reports of acute kidney injury with frequent use. In all cases, renal dysfunction was temporary and did not require maintenance dialysis. There have been no previous reports of irreversible renal dysfunction after a single dose of oxaliplatin. CASE PRESENTATION: Previous reports of oxaliplatin-induced renal injury occurred after patients received multiples doses. In this study, a 75-year-old male with unknown primary cancer and underlying chronic kidney disease developed acute renal failure after receiving the first dose of oxaliplatin. Suspected of having drug-induced renal failure through an immunological mechanism, the patient was treated with steroids; however, treatment was ineffective. Renal biopsy ruled out interstitial nephritis and revealed acute tubular necrosis. Renal failure was irreversible, and the patient subsequently required maintenance hemodialysis. CONCLUSIONS: We provide the first report of pathology-confirmed acute tubular necrosis after the first dose of oxaliplatin which led to irreversible renal dysfunction and maintenance dialysis.

Renal Biopsy Diagnosis of Acute Tubular Injury after Pfizer-BioNTech COVID-19 Vaccination: A Case Report.

Coronavirus disease 2019 (COVID-19) is a severe respiratory infection that can be fatal in unvaccinated individuals; however, acute kidney injury (AKI) is a rare adverse reaction to COVID-19 vaccination. AKI resulting from multiple conditions can have severe consequences, including end-stage renal failure, if not treated with immunosuppressive agents. However, acute tubular injury (ATI) as the sole cause of AKI has not been previously reported. Herein, we discuss an obese 54-year-old man with type 2 diabetes who received four COVID-19 vaccines; three from Pfizer and one from Moderna. Diabetic retinopathy, urinary protein, and occult blood were absent with no other underlying diseases. There was no history of COVID-19 infection. He was referred to our hospital 5 days after receiving the fourth Pfizer-BioNTech COVID-19 vaccine dose with stage 3 AKI. Urinary findings revealed new proteinuria and glomerular occult blood. Physical examination and infection testing were unremarkable. Steroids were introduced on admission for rapidly progressive glomerulonephritis. A renal biopsy performed on Day 2 revealed only ATI. Therefore, steroids were discontinued on Day 5, after which renal function recovered spontaneously, and urinalysis abnormalities disappeared. Renal function remained normal during follow-up. We report a case of AKI with severe renal dysfunction after COVID-19 vaccination, wherein renal biopsy effectively determined the disease status (ATI), which did not require immunosuppressive treatment.

Serum Uromodulin Is a Possible Auxiliary Diagnostic Tool for Acute Tubular Injury and Acute Interstitial Nephritis: A Case Series.

Recently, the usefulness of serum uromodulin (sUmod) as a novel renal biomarker has been attracting attention. Clinical evidence regarding sUmod measurements has been accumulated by analyzing cross-sectional data. However, little is known about the longitudinal data on sUmod. Therefore, we decided to investigate the variability of sUmod in patients with acute kidney injury due to different causes. High concentrations of sUmod have been observed in patients with acute tubular injury (ATI) and/or acute interstitial nephritis (AIN). sUmod could be used as an auxiliary diagnostic tool for ATI and AIN.

Combining Clinical Parameters and Acute Tubular Injury Grading Is Superior in Predicting the Prognosis of Deceased-Donor Kidney Transplantation: A 7-Year Observational Study.

Background: We developed a pragmatic dichotomous grading criterion to stratify the acute tubular injury (ATI) of deceased-donor kidneys. We intended to verify the predictive value of this criterion for the prognosis of deceased-donor kidney transplantation. Methods: The allografts with ATI were classified into severe and mild groups. Severe ATI was defined as the presence of extreme and diffuse flattening of the tubular epithelial cells, or denudement of the tubular basement membrane. The clinical delayed graft function (DGF) risk index was calculated based on a regression model for posttransplant DGF using 17 clinical parameters related to donor-recipient characteristics. Results: A total of 140 recipients were enrolled: 18 severe and 122 mild ATI. Compared with the mild ATI group, the severe ATI group had more donors after cardiac death, higher median donor terminal serum creatinine level (dScr), and longer median cold ischemia time. Severe ATI had a higher DGF rate (55.6% vs 14.6%, p < 0.001), longer DGF recovery time (49.6 vs 26.3 days, p < 0.001), and a lower estimated glomerular filtration rate (eGFR) at 1 month (23.5 vs 54.0 ml/min/1.73 m2, p < 0.001), 3 months (40.4 vs 59.0, p = 0.001), and 6 months after transplant (46.8 vs 60.3, p = 0.033). However, there was no significant difference in eGFR at 1 year or beyond, graft, and patient survival. The predictive value of combined dScr with ATI severity for DGF rate and DGF recovery time was superior to that of dScr alone. The predictive value of the combined DGF risk index with ATI severity for DGF was also better than that of the DGF risk index alone; however, the association of the DGF risk index with DGF recovery time was not identified. Chronic lesions including glomerulosclerosis, interstitial fibrosis, arterial intimal fibrosis, and arteriolar hyalinosis were associated with declined posttransplant 1-year eGFR. Conclusion: Based on our pragmatic dichotomous grading criterion for ATI in a preimplantation biopsy, donor kidneys with severe ATI increased DGF risk, prolonged DGF recovery, and decreased short-term graft function but demonstrated favorable long-term graft function. Our grading method can offer additive valuable information for assessing donor kidneys with acute kidney injury and may act as an effective supplementary index of the Banff criteria.

ACE2 Promoted by STAT3 Activation Has a Protective Role in Early-Stage Acute Kidney Injury of Murine Sepsis.

Sepsis-induced AKI (SIAKI) is the most common complication with unacceptable mortality in hospitalized and critically ill patients. The pathophysiology of the development of SIAKI is still poorly understood. Our recent work has demonstrated the role of signal transducer and activator of transcription 3 (STAT3) pathways in regulating inflammation and coagulation in sepsis. We hypothesized that STAT3 activation has a critical role in early-stage SIAKI. The early-stage SIAKI model was established in cecal ligation and puncture (CLP) mice, which recapitulates the clinical and renal pathological features of early-stage AKI patients. Brush border loss (BBL) was the specific pathological feature of acute tubular injury in early-stage AKI. The role of STAT3 signaling and angiotension system in early-stage SIAKI was evaluated. The STAT3 activation (increased pSTAT3) and increased angiotensin-converting enzyme 2 (ACE2) expressions were observed in CLP mice. The low responsive expressions of pSTAT3 and ACE2 to septic inflammation in CLP AKI mice were associated with BBL. Correlation analysis of proteins' expressions showed pSTAT3 expression was significantly positively related to ACE2 expression in CLP mice. Reduced pSTAT3 after S3I201 intervention, which blocked STAT3 phosphorylation, decreased ACE2 expression, and exacerbated tubular injury in early-stage SIAKI. Our data indicate that endogenous increase of ACE2 expression upregulated by STAT3 activation in early-stage SIAKI play protective role against acute tubular injury.

Concomitant Identification of Muddy Brown Granular Casts and Low Fractional Excretion of Urinary Sodium in AKI.

Background: Fractional excretion of urinary sodium (FENa) is a widely utilized clinical test to evaluate acute kidney injury (AKI). A low FENa (<1%) is deemed consistent with prerenal azotemia and inconsistent with acute tubular injury (ATI). Muddy brown granular casts (MBGC) on microscopic examination of urinary sediment (MicrExUrSed) are highly suggestive of ATI. We hypothesized that there is poor concordance between the presence of MBGC and FENa in ATI. Methods: We conducted a prospective observational study in patients with AKI seen during inpatient consultation. We extracted patients who underwent assessment of percentage of low power fields (LPFs) with MBGC by MicrExUrSed and concomitant measurement of FENa. Diagnostic concordance between MBGC and FENa and their individual prognostic value were examined. Results: Our cohort included 270 patients, 111 (41%) of whom were women. Median age was 61 years (range 27-92 years), and median serum creatinine was 3.7 mg/dl ( range1.2-22.0 mg/dl). MBGC were found in 49% (133/270). FENa <1% (inconsistent with ATI) was found in 50/133 (38%), 38/115 (33%), and 16/45 (36%) of those with >0%, ≥10%, and ≥50% LPFs with MBGC, respectively. Concordance between FENa and MBGC for ATI diagnosis was deemed fair (estimated κ-coefficient=0.2), and poor (κ=-0.11) within a subgroup of patients with preexisting chronic kidney disease (n=139). In patients with biopsy-proven ATI (n=49), MBGC had 100% specificity and 100% positive predictive value for ATI. MBGC were associated with greater risk for ≥50% increase in creatinine from baseline at discharge (acute kidney disease [AKD]). Conclusions: About two of five patients with MBGC identified by MicrExUrSed presented with FENa <1%. Presence of MBGC was consistent with ATI, as verified by biopsy, and were predictive of AKD. These data suggest that the sole reliance in low FENa to exclude ATI should be abandoned, and MicrExUrSed should be pursued for AKI diagnosis.