Thread by @BagaiDr

Kidney damage asso with COVID19: from acute to chronic phase; most common form of glomerular injury is collapsing glomerulopathy (CG), strongly asso with apolipoprotein L1(APOL-1) risk variants; acute lesions, are secondary to direct or indirect effects, tandfonline.com/doi/full/10.10…

progress to chronicity; specific to long COVID-19 in absence of any other cause. Residual inflammation asso with SARS-CoV-2 infection, add to (AKI) as transitional state with or without severe histological lesions,responsible for greater kidney funct⬇️in mild-to-moderate COVID19

Various meta-analyses on AKI asso with COVID-19 (COV-AKI)- frequency between 10 and 17%, with a wide range between 0.5% and 80.5%; Chinese study, detection rate of AKI was 0.99%. After adjusting for frequency of serum creatinine testing, incidence of AKI⬆️to 11.6%.

population in relation to severity of disease (virulence of SARSCOV2 variant asso with COVID19 wave, burden of comorbidities [age,CKD, heart failure,DM, arterial hypertension, obesity], genetic predisposition [APOL-1 polymorphism], admission to ICU, ventilation- prone position);

incidence of AKI of 46% with 19% replacement therapy; incidence of 76% admit to ICU, 32% dialysis. impact of prone position used in (ARDS) on occur of AKI in COVID19,BMI. prone position responsible for⬇️in GFR lead to AKI. AKI was more common in ARDS (68% vs 53.6%, p < 0.001),

ventilation (91.9% vs 77.7%, p < 0.001), and even more so in those in the prone position (74.8% vs 61%, p < 0.001).
incidence, severity of AKI (AKI requiring dialysis) ⬇️over time & across COVID19 waves, first wave being more severe ;

⬇️in virulence of SARSCoV2 due to multiple mutations & vac in collective immunity beyond natural infection;
incidence- severity of COV-AKI ⬆️ other settings as community acquired pneumonia or sepsis.
overall incidence of AKI of 16%. incidence⬆️ to 26.2% in COVID19 vs 12.4%;

asso COVID19 with non-COVID19 respiratory infections, report⬆️incidence in COVID19, 30% vs 12%; dialysis was⬆️in COVID19 4.4% vs 0.9%;
time of onset AKI, start of dialysis relative to date of admission, & % of kidney function recovery-severity of renal lesions asso with SARSCoV2

median duration of AKI onset of 1d with median time from diagnosis to dialysis initiation of 3d; kidney function recovery of about 65%, a low rate when compared to other causes where frequency of recovery is 80% with median duration of 10d;
AKI a strong predictor of mortality;

AKI ⬆️risk of mortality by 3x in infected SARSCOV-2.
risk was⬆️for stages 2 and 3, but also when AKI asso with COVID19 vs other causes. usual limitations of creatinine in early detection of AKI- use of biomarkers; COVID19, biomarkers of AKI: functional biomarkers (cystatin c),

damage biomarkers (kidney molecule injury 1: KIM-1, l-type fatty acid binding protein: L-FABP, interleukin 18: IL-18, soluble urokinase-type plasminogen activator receptor: suPAR, neutrophil gelatinase associated lipocalin: NGAL),

stress biomarkers (tissue inhibitor of metalloproteinase 2: TIMP-2 and insuline-like grow factor binding protein 7: IGFBP7) are effective in detecting AKI

Kidney damage associated with COVID-19: from the acute to the chronic phase.

rapid clearance of virus in kidney tissue; Detection of SARSCoV 2 be reduced over time, median time to clearance of SARSCoV2 varies from 11 to 24d, median time between symptoms and kidney biopsy was several weeks,(had negative(RT-PCR);
direct cytopathic effects of SARSCoV2 due to

entry- replication of virus in renal cells, altering several regulatory pathways, renin-angiotensin-aldosterone system (RAAS), repercussions on kallikrein-kinin system (KKS);
downregulation of ACE2 by CoV2 entry into the intracellular medium favors accumulation of

circulating angiotensin II, vasoconstrictive, profibrotic and pro-inflammatory effects,⬇️renal blood flow, allowing ischemia to occur.
damage caused by direct cytopathic effects of SARSCoV-2 among host renal cells, virus induce exaggerated systemic immune response,

hypercytokinemia or cytokine storm, haemodynamic changes, exaggerated recruitment of pro-inflammatory cells, generation of reactive oxygen species (ROS), dysregulation of complement system and coagulopathies (mediated by tissue factor pathway),kidney parenchymal involvement,

endothelial damage and severe effects on kidney function; cytokine storm secondary to late type I (IFN-I) signaling induced by SARSCoV2,⬆️ accumulation of macrophages-monocytes, result⬆️levels of pro-inflammatory cytokines-chemokines or lymphopenia, marker of immune dysregulation

Rhabdomyolysis an indirect effect of SARSCov2 asso with AKI;
These factors specific to COVID19 interact with usual risk factors for AKI as hemodynamic instability, hypoxia and sepsis,⬆️by use of nephrotoxic drugs as contrast agents, (NSAIDs), aminoglycosides, vancomycin.

Several risk factors for COV-AKI. comorbidities (advanced age, CKD, heart failure, etc.), mechanical ventilation were risk factors for AKI.
Beyond severity of disease by hypoxia with or without need for ventilator support, drug toxicity, related to vancomycin, risk factor

proteinuria varies widely between 24% & 84% with or without AKI; incidence of proteinuria (semi quantitative proteinuria ≥2 +) was 8% vs. 30%, in no AKI vs. AKI group;
proteinuria/creatinuria (P/C) ratio, incidence of 0.6% vs 3%. resolution of proteinuria in COVID19

with median duration of 12d in 69%, transient nature of proteinuria. proteinuria is of tubular origin. proteinuria in COVID19 report out of 24 electrophoreses, 17 were of tubular origin (albuminuria < 50%), 7 cases had mixed proteinuria (albuminuria between 50 and 80%);

specifically report 1 α-microglobulin as the main tubular proteinuria in COVID19; Proteinuria of glomerular origin strongly asso with collapsing glomerulopathy;
Proteinuria reflects dysfunction of glomerular membrane permeability or dysfunction of reabsorption by PCT epithelial;

COVID19, disruption of glomerular capillary wall may result in COVID asso nephropathy (COVAN), impairment of tubular reabsorption during acute tubular injury . Systemic inflammatory response lead to⬆️ glomerular permeability for proteinuria & preexisting CKD

other factors implicated in multifactorial pathogenesis of proteinuria in COVID19;
Beyond its high frequency, proteinuria during COVID-19 has predictor of mortality asso with or without AKI &/or microscopic hematuria.
admission urine screen for nephritic syndrome

tubular proteinuria (median P/C ratio, 0.7 g/g) in 80% of patients, associated with tubular leakage of uric acid (46%), phosphorus (19%), without urinary glucose loss; (46%) had a urinary leakage of neutral AA. uric acid excretion >10% in presence of hypouricemia;

acute incomplete Fanconi syndrome in admitted with mild, moderate, or severe COVID;
75% had at least two of four defining elements of renal Fanconi syndrome (renal phosphate leakage, normoglycemic glycosuria, hyperuricosuria, proteinuria). main abnormalities: proteinuria (88%),

renal phosphorus leakage (55%), hyperuricosuria (43%) and normoglycemic glycosuria (30%); admitted ICU hv more severe forms of Fanconi syndrome. tubulopathy preceded AKI &⬇️ in renal recovery phase. tubular dysfunction was asso with severity of COVID19 with⬆️risk of resp failure

biological abnormalities (renal phosphate leakage, normoglycemic glycosuria, hyperuricosuria, proteinuria) are asso with structural lesions of proximal tubule on postmortem kidneys from COVID19;
consistent tubular damage, necrosis, loss of brush border of proximal tubule,

signif⬇️ (50%) in megalin receptor expression. unusual particles as direct infection [
normal structures;
SARS-CoV-2 directly infect proximal tubular cells via ACE2R, causing proximal tubular dysfunction. toxicity of drugs in COVID19. osmotic tubulopathy in remdesivir use

Angiotensin-converting enzyme 2 (ACE2), ligand for viral cell invasion is expressed on both proximal, distal tubular cells; distal involvement in context of COVID19. nephrogenic diabetes insipidus in context of COVID19. Renal tubular acidosis with hyperkalemia in heparin use

⬆️% of severe AKI (7% vs 1%) and non-recovery of kidney function at discharge (70% vs 56%) in COVID19 than admitted for Haemophilus influenza;
low rate of short-term recovery of kidney function in COVID19;
COVID19 is likely to have⬇️nephron reserves (elderly, comorbid [HT,DM]).

decline in kidney function over long-term period of 6mth. 35% of discharged following COVID19 had a progressive⬇️in kidney function at 6mth, (GFR) < 90 mL/min; 28.5% of hospitalized for COVID19 had GFR of < 90 mL/min at 1 year after discharge,
rate of⬇️in kidney function in

COVID19 depends on basis of COVID-19 severity asso or not with AKI, compared with other causes of AKI, rate more pronounced in COVID-AKI;
GFR⬇️rate varied from −3.26 in non-hospitalized, −5.2 in hospitalized to −7.69 mL/min/1.73m2/yr in (ICU);

AKI status, COV-AKI had⬇️⬇️in eGFR after adjustment for baseline comorbidities (−12. 4 mL/min/1.73 m2/year) and that this decline was faster in patients with COV-AKI compared to non-CoV-AKI ; Advanced age,severe AKI, HT, male as risk factors for progression to CKD after COV-AKI

Apart from AKI, post-COVID-19 state involve a risk of decline in kidney function. comorbidities as hypertension, diabetes mellitus and dyslipidemia in post-COVID-19 could not only participate in development of CKD,subclinical manifestation of CKD

several direct or indirect effects of SARS-Cov-2 infection persist during post-discharge recovery,lead to recurrence of septic,AKI episodes &⬆️ risk of CKD.
mechanisms to CKD post COVID19 as unresolved tubular lesions,micro/macro vascular lesions, podocytopathies,collapsing