• Sudha Mannemuddhu MD & Gerren Hobby MD

KI Reports Top 10 Articles for 2021

Updated: Mar 18

Summaries by Gerren Hobby (@ghobby) and S. Sudha Mannemuddhu (@drM_sudha)

CNN Model for AKI prediction in intensive care units

Acute kidney injury (AKI) is common among hospitalized patients, with up to 70% incidence in the critically ill. AKI is associated with significant morbidity and mortality. Its complex nature, multiple etiologies, inconsistencies in staging and scoring, has led to delays in diagnosis and treatment, and underappreciation of incidence and prevalence. The most widely utilized marker of kidney function, serum creatinine (sCr), is suboptimal in AKI detection, as detectable increases are only observed ~24 hours following initial injury. The search for alternative markers and strategies to identify AKI early continues as early identification and prompt treatment have shown to improve patient outcomes in select populations. Machine learning is one of the newest avenues pursued by AKI enthusiasts. This single-center study conducted between 2001 to 2012 in Beth Israel Deaconess Medical Center in Boston, Massachusetts utilizes data from the multiparameter intelligent monitoring in intensive care (MIMIC-III) version 1.3 data set and describes a methodology for the development of a convolutional neural net (CNN) prediction system. The CNN prediction system retrospectively analyzed a total of 12,347 patient encounters from the MIMIC-III database and predicted the onset of AKI stage 2 or 3 per KDIGO guidelines. It was compared with the XGBoost AKI prediction model and the sequential organ failure assessment (SOFA) scoring system. Interestingly and fortunately, the CNN model does not require SCr or urine output values. On a hold-out test set, the CNN algorithm attained an AUROC of 0.86 and PPV of 0.24, relative to a cohort AKI prevalence of 7.62%, for long-horizon AKI prediction at a 48-hour window before onset. A CNN machine learning-based AKI prediction model outperformed its comparators in predicting AKI 48 hours before onset, without reliance on SCr measurements. This could open new avenues in the diagnosis and management of AKI.

Visual abstract by @krishnadoctor

Is telemedicine a good alternative care strategy for CKD and kidney transplant population?

Though tele video conferencing (TVC) was used as an alternative health care strategy, it was not popular until the COVID-19 pandemic, after which its use increased exponentially. Many practices adapted to the social distancing and adopted telemedicine to varying degrees. This single-center Australian prospective, 2-year longitudinal, case-control study not only looked into the utilization of TVC in Chronic kidney disease (CKD) and kidney transplant recipient (KTR) population, but also assessed the feasibility, sustainability, and clinical outcomes of TVC. A total of 64 CKD or KTR patients, 32 per group (telemedicine and control), were recruited. They were age, sex and CKD.KTR status matched.TVC uptake was 71 % in the first year but decreased to 50% in the second year. TVC was found to be sustainable and decreased travel distance by 48% and 37% in the first and second years, respectively. More importantly, there were no significant differences in blood pressure, kidney function, or hospitalizations between the groups. Patient satisfaction was high and similar in both groups. This study highlighted the feasibility of telemedicine and similar outcomes compared to those of standard care for KTRs and CKD patients suggesting that telemedicine can and should be embraced by nephrology practices.

Visual abstract by @krishnadoctor1

What are the adverse graft related events of blood transfusion after kidney transplant?

The risk of sensitization to HLA due to exposure to non-self-human leukocyte antigens (HLA) via multiple red blood cell transfusions (RBCTs) and the development of anti-HLA antibodies is a well-known phenomenon. Theoretically, a kidney transplant recipient (KTR) can develop donor-specific antibodies against the kidney allograft donor, when exposed to non-self HLA antigens from a RBCT. However, this is not consistently described in the literature and KDIGO guidelines do not provide recommendations on RBCTs. This Canadian retrospective study examined the risk of adverse graft outcomes in post-kidney transplant RBCT in adult KTR from 2002-2018, with a median follow-up of 3.8 years. This study also categorized the RBCT exposure as 1, 2, 3 to 5, and >5 transfusions. Rejection and death-censored graft loss (DCGL) were the outcomes of interest. RBCT occurred in 37% with a total of 2373 RBCTs. RBCT after kidney transplant is not associated with rejection but may carry an increased risk for DCGL. Despite being a retrospective study, this is an important study as it sheds light on the potential immunomodulatory effects of RBCT in KTR.

Visual abstract by @aakashshingada

How safe and useful is Remdesivir in kidney transplant recipients with COVID-19 infection?

The COVID-19 pandemic has evolved along with our available treatment strategies. The required immunosuppressant therapy in kidney transplant (KT) population demanded close attention to potential drug interactions and/or adverse reactions with cumulative toxicities with the addition of beneficial COVID-19 therapies. In this multicenter study from the Spanish registry, 51 KT recipients who developed COVID-19 infection and received remdesivir were studied. The mean time from admission to remdesivir treatment was 2 days. About half (55%) needed mechanical ventilation and the mortality rate was 19%. The remdesivir did not have kidney or hepatic toxicity and its use decreased the incidence of acute kidney injury (AKI) from 50% to 28% . This is one of the largest studies demonstrating remdesivir is well tolerated and safe in the KT population.

Visual abstract by @EricAu

Usefulness of Apheresis in the treatment of idiopathic nephrotic syndrome in native kidneys

Idiopathic Nephrotic Syndrome (INS) accounts for 20% of glomerular disease in adults, yet, pathogenesis is an enigma. Histopathology suggests that one or more putative circulating factors might be the cause, which led to a search for alternative treatment strategies, particularly when first (steroids) and second-line (steroid-sparing agents) modalities fail. The recent evidence made it clear that apheresis is the gold standard treatment for recurrent INS after transplant which begs the question; can apheresis be a treatment choice for adults with refractory INS in native kidneys? In this retrospective study by Moret et al, 21 patients with INS (12 with FSGS and 9 with minimal change disease), 16 years and older received at least 3 sessions of apheresis (Plasma exchange, immunoadsorption, LDL-apheresis, double-filtration plasmapheresis, etc) and were followed for at least 3 months. At 12 months follow-up, 33% (7/21) achieved remission. Diagnosis within 1-year of initiation of apheresis, age of 50 years or younger, decrease in proteinuria between time of diagnosis and apheresis initiation, and need for dialysis before apheresis were associated with remission. It was interesting to note that 3 out of 7 patients on dialysis became dialysis-free. This study highlights that apheresis may result in remission in adult patients with refractory INS (particularly, at risk for kidney failure) if initiated early.

Visual abstract by @EricAu

How Does Complement C3 Deposition on Kidney Biopsy Affect Long Term Survival in ANCA Vasculitis Patients

ANCA vasculitis is one of the more common glomerulonephritides. It is characterized by a pauci-immune pattern with necrotizing crescentic lesions on the kidney biopsy and the complement system has historically been considered to have a limited role. Over the past several years, animal studies have suggested a more prominent role for the complement pathway. Clinical observations have also shown C3 deposition in 30-40% of ANCA GN cases, which are associated with a higher number of cellular crescents. Other studies have shown that patients with ANCA vasculitis and low serum C3 levels at diagnosis have worse renal outcomes and survival rates. Despite this, the clinicopathologic significance of complement deposition has not been fully characterized. This study retrospectively identified 142 patients with ANCA glomerulonephritis and examined them for C3 deposition. In this study, C3 deposition was observed in 56 of the 142 kidney biopsies. Patients with C3 deposition had lower serum C3 levels. At a median follow-up of 2.9 years, it was found that those with C3 deposition on immunofluorescence was associated with increase in the primary composite endpoint of a 30% reduction in eGFR, ESKD, and death. This association remained even when adjusting for age, sex, baseline eGFR, serum C3 level, immunosuppression, and other kidney biopsy characteristics (percentage of normal glomeruli, cellular crescents, global sclerosis, and interstitial damage). This study shows that C3 deposition on kidney biopsies in ANCA vasculitis patients is associated with a more aggressive clinical course regardless of other clinical and histologic features. This study adds to our understanding of long-term prognosis in these patients.

Visual abstract by @edgarvlermamd

Is Albuminuria Associated with Pathological Diabetic Nephropathy Lesions?

Diabetic kidney disease (DKD) accounts for almost half of the cases of end-stage kidney disease in the world. The traditional paradigm is that diabetic kidney disease progresses from microalbuminuria, followed by macroalbuminuria, which is followed by a decline in kidney function. Another standard tenet of DKD has been that pathologic diabetic nephropathy lesions progress with increasing albuminuria. Contemporary thought has challenged the first view and shifted it towards a realization that diabetic kidney disease can progress towards ESKD even without increasing proteinuria. Additionally, recent studies have suggested that albuminuria is not linked with pathologic diabetic nephropathy lesions. This study better characterized this association by examining 106 autopsy cases with diabetes in a Japanese community. The mean age of these patients was 76 years old. The patients were split into three groups with ACR values of <30mg/g, 30-299mg/g, and finally at least 300mg/g. The kidney biopsy specimens were categorized into the standard classes for diabetic nephropathy lesions according to the criteria of the Renal Pathology Society.

  • Class I - mild or nonspecific LM changes and EM-proven GBM thickening

  • Class IIa - mild mesangial expansion

  • Class IIb - severe mesangial expansion

  • Class III - modular sclerosis (Kimmelstiel-Wilson lesion)

  • Class IV - advanced diabetic glomerulosclerosis

Overall, it was found that the frequency of class IIa or higher diabetic glomerular lesions were present in 63% of cases and the frequency of diabetic lesions on a kidney biopsy were higher with higher levels of albuminuria. Additionally, the presence of class IIa lesions or higher was present in 51.2% of patients with ACT values of <30mg/g. This study helped advance our understanding of the most common cause of ESKD, showing that diabetic nephropathy lesions are in fact associated with albuminuria, but that a high percentage of patients have histological lesions in the absence of increased albuminuria.

Visual abstract by @HelloKidneyMD

What is Risk of Major Bleeding of Transjugular Native Kidney Biopsies?

Kidney biopsies are performed via percutaneous or transjugular routes. In some patients, especially those with the highest need for a kidney biopsy, comorbidities such as thrombocytopenia, antiplatelet agents or anticoagulation can prevent people from getting a kidney biopsy due to undue risk. Despite that the first transjugular biopsies were performed in the 1990s, the exact risk of major bleeding was relatively unknown as data was derived from a few small case studies. In those studies, the major rate of complications varied from zero to 25%. This study aimed to better characterize bleeding risk by examining 60,331 patients, among which 5,305 underwent a transjugular kidney biopsy and 55,026 patients underwent percutaneous kidney biopsies. In those at lowest risk, major bleeding occurred in 0.4% vs 0.5% for transjugular vs percutaneous biopsies. In the highest risk group, major bleeding occurred in 19.1% vs 30.8% in transjugular vs percutaneous approaches with an odds ratio for major bleeding of 0.83 [95% CI 0.72-0.96]. This is a useful study that better delineates the risk of bleeding from two approaches for kidney biopsies. In addition, a risk score originally developed to assess the risk of major bleeding in percutaneous kidney biopsies was also found to be useful for transjugular approach risk assessment.

Visual abstract by @krishnadoctor1

What Mesangial Cell Surface Protein is Responsible the Development of Light Chain Deposition Disease and AL Amyloidosis?

During the normal production of immunoglobulins, there is a 30-40% excess production of free light chains (fLCs). These excess fLCs are efficiently cleared from the blood via endocytosis in the proximal tubule through actions of megalin and cubilin. In the setting of monoclonal gammopathies, most fLCs are nephrotoxic. Of these nephrotoxic fLCs, around 70% cause tubular damage, but the other 30% interact with the glomerular mesangial cells to trigger light chain deposition disease (LCDD) or AL amyloidosis. From a pathophysiological standpoint, these two end destinations are quite different. A transition of mesangial cells from a smooth muscle phenotype to a myofibroblast type is a tenant of the development of LCDD. In contrast, AL amyloidosis requires the endocytosis and transport of fLCs into mature lysosomes to produce amyloid fibrils. In order for either of these two processes to occur, fLCs must interact with a surface protein. Since megalin and cubilin are not present on mesangial cells, the identity of this surface protein was unknown as were the mechanisms by which it facilitates the development of LCDD or AL amyloidosis. In this study, fLCs were collected from the urine of patients with LCDD or AL amyloidosis, and were incubated with mesangial cells. Utilizing multiple experiments, it was shown that these fLCs interact with the protein, sortilin-related receptor (SORL1), on the mesangial cell surface. In LCDD, the interaction of fLCs with SORL1 and caveolin 1 (CAV1) results in nuclear signaling to activate c-FOS and this results in the mesangial cell transition to a myofibroblast phenotype. Conversely, in AL amyloidosis, fLCs interact with SORL1 causing their interalization into endosomes with subsequent transport into mature lysosomes where amyloid fibrils are produced. This paper identifies SORL1 and the surface protein responsible for these two cellular fates as well as insight into the mechanism for LCDD and AL amyloidosis phenotypes.

Visual abstract by @krithicism

Does Finerenone Provide Any Additive Benefit to Sodium-Glucose Cotransporter-2 Inhibitor Therapy in Slowing CKD Progression?

SGLT2 inhibitors have ushered in a new era for treatment of diabetic kidney disease and proteinuric non-diabetic kidney disease. More recently, finerenone has entered the scene as a nonsteroidal mineralocorticoid antagonist that targets inflammatory and fibrotic pathways in CKD. In 2020, the FIDELIO-DKD Study was published and showed that finerenone reduced CKD progression and cardiovascular deaths in adults with diabetic kidney disease. A subset of the patients in this trial were also on an SGLT-2i at baseline. The authors of this KI Reports study – Rossing, et al sought to investigate an additive effect of finerenone in addition to SGLT-2i use in these patients. Of the 5674 patients in the FIDELIO-DKD study, 259 (4.6%) were also on an SGLT-2i at baseline. The outcomes in the Rossing, et al study used the same primary and secondary outcomes as the FIDELIO-DKD study:

  • Primary kidney outcome: a time-to-event analysis using the composite outcome of kidney failure, a sustained decrease of 40% or more in eGFR from baseline (for ≥4 weeks), or death owing to renal causes (renal death). Kidney failure was defined as end-stage kidney disease or an eGFR <15 ml/min per 1.73 m2, confirmed by a second measurement at the earliest 4 weeks after the initial measurement.

  • Key secondary outcome: a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.

Finerenone was found to reduce both the primary and secondary outcomes as well as reduce UACR regardless of baseline SGLT-2i use. Since type 2 diabetic kidney disease is the leading worldwide cause of CKD, the addition of a medication which specifically targets inflammatory and fibrotic pathways in CKD is an important step in advancing care for this population.

Visual abstract by @Sophia_kidney

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