Approach to the Patient with Kidney Disease PDF

Approach to the Patient with Kidney Disease: Acute and Chronic Kidney Diseases & Glomerular and Tubulointerstitial Disorders GENERAL PATHOLOGY 3º Prof. Luis D’Marco, MD, MSc, PhD.  The kidneys The kidneys play a central...

Approach to the Patient with Kidney Disease: Acute and Chronic Kidney Diseases & Glomerular and Tubulointerstitial Disorders GENERAL PATHOLOGY 3º Prof. Luis D’Marco, MD, MSc, PhD.  The kidneys The kidneys play a central role in the excretion of many metabolic breakdown products, including ammonia, urea, creatinine, uric acid, drugs and toxins. The kidneys make large volumes of ultrafiltrate of plasma (120 mL/min, 170L/24h) at the glomerulus, and selectively reabsorb components of this at points along the nephron. The rates of filtration and reabsorption are controlled by many hormonal and haemodynamic signals to regulate fluid and electrolyte balance, BP, and A-B and Ca-P homeostasis. The kidneys activate VitD and control the synthesis of red blood cells by producing EPO.  The kidneys The kidneys have a rich blood supply and receive approx. 20–25% of cardiac output through the renal arteries, which arise from the abdominal aorta. Functional anatomy of the kidney glomerulus Glomerular architecture glomerulus afferente efferente arterio/ peritubular arteriol ! spe kidney cells filtration barrier : fenestration endothelium ; basement mb ; podocyte (epithelial visceral c) ; mesengial c (join everything together) ; juxtaglomerular (renin dep of NA/Cl concentration)  Glomerular architecture fenestration inside of art small art generating glomerulus bowmann space with podocytes Clinical examination techniques to evaluate renal abnormalities Serum creatinine and the GFR serum creatinine high = filtration glomerus rate = down less creatinine = 0.9 creatinine = normal = high filtration 7 creatinine = down filtration not only creatinine must evaluate with formula Renal ultrasound  Técnicas de imagen D’Marco, et al. Kidney Res Clin Pract 2019;38(3):365-372 Eisner, et al. Surg Radiol Anat (2010) 32:879–882 Chughtai, et al. Hypertension. 2010;56:901-906  Técnicas de imagen Fried, J, et al. Am J Kidney Dis. 2019 Tomografía renal Fried, J, et al. Am J Kidney Dis. 2019 Retrograde pyelography & DMSA radionuclide scan Nephritic and nephrotic syndrome  Glomerular diseases Most patients with glomerular disease do not present acutely and are asymptomatic until abnormalities are detected on routine screening of blood or urine samples. There are many causes of glomerular damage, including immunological injury, inherited diseases (Alport’s syndrome), metabolic diseases (diabetes), and deposition of abnormal proteins such as amyloid in the glomeruli. Glomerular cell types may be the target of injury. Proteinuria is the hallmark of glomerular disease; however, the response of the glomerulus to injury and hence the predominant clinical features vary according to the nature of the insult, ranging from fulminant nephrotic syndrome to rapidly progressive glomerulonephritis. Several prognostic indicators are common to all causes of glomerulonephritis and may help assess the need for immunosuppressive therapy.  Glomerular diseases Nephritic syndrome: Is characterized by the presence of haematuria in association with hypertension, oliguria, fluid retention and reduced/declining renal function. Nephrotic syndrome: Is characterized by very heavy proteinuria (> 3.5 g/24 hrs), hypoalbuminaemia and oedema. Blood volume may be normal, reduced, or increased. Renal sodium retention is an early and universal feature. Many patients with GN, particularly those with milder disease, do not exhibit all of these features; their combined presence, however, is typical of a rapidly progressive glomerulonephritis and warrants urgent investigation.  The glomerulus is injured by a variety of mechanisms subendothelial = Ab subepithelial immune deposite / inflamatory element = glomerulo nephritis Nephritic and nephrotic syndrome most common nephritis = Berger d main nephrotic infectious minimal changes d more nephritic focal and segmental could have both dislipidemia = increase in lipid-protein (liver see decrease in protein = production or all proteins even lipidic ) Histopathology of glomerular disease area affected astherosclerosis no blood supply Berger d Investigation of haematuria NVH = non-visible haematuria Causes of haematuria Investigation of nephritic síndrome & Urine microscopy red c cast Investigation of proteinuria diabetes = higher proteinuria (normal) Consequences of the nephrotic syndrome and their management Edema Poor prognostic indicators in glomerular disease Male sex Hypertension Persistent and severe proteinuria Elevated creatinine at time of presentation Rapid rate of decline in renal function Tubulo-interstitial fibrosis observed on renal biopsy Acute kidney injury (AKI)  Acute kidney injury (AKI) Describes the situation where there is a sudden and often reversible loss of renal function (days or weeks) and is usually accompanied by a reduction in urine volume. Approx. 7% of all hospitalized patients and 20% of acutely ill patients develop AKI. In uncomplicated AKI mortality is low, even when RRT is required. In AKI associated with sepsis and multiple organ failure, mortality is 50–70% and the outcome is usually determined by the severity of the underlying disorder and other complications, rather than AKI itself. Elderly patients are at higher risk of developing AKI and have a worse outcome.  Pathophysiology There are many causes of AKI and it is frequently multifactorial. It is helpful to classify it into three subtypes: diarrhea dehydratation ; if nothing done = renal issue ‘Pre-renal’: when perfusion to the kidney is reduced. ‘Renal’: when the primary insult affects the kidney itself. ‘Post-renal’: when there is obstruction to urine flow at any point from the tubule to the urethra. Phases of AKI  Renal haemodynamics and autoregulation of GFR abuelos = not take a lot of painkiller painkiller = afferent constrition ; efferent vasodilation = less filtration avoiding in elderly patients  Acute kidney failure destruction of the tubule wall = inflammation = create a cast (with protein Tamm-Horsfall) = reduction of the flow Classification of AKI  Management of acute kidney injury decrease hydratation and fluid intake Assess fluid status as this will determine fluid prescription:  If hypovolaemic: optimise systemic haemodynamic status with fluid challenge and inotropic drugs if necessary. digoxine = increase P myocardium  Once euvolaemic, match fluid intake to urine output plus an additional 500mL to cover insensible losses. insensible loss= sweat, breathing  If fluid-overloaded, (prescribe loop diuretics); if the response is unsatisfactory, HD may be required. Administer calcium to stabilize myocardium and glucose and insulin to correct hyperkalemia if K+ >6.5 mmol/L dialysis or restoration of renal function. Sodium bicarbonate to correct acidosis if pH kidneys = cell damage = nephritis  Acute interstitial nephritis breaking of the tubule  Scattered breaks (B).  The interstitium (I) is edematous and infiltrated by inflammatory cells.  Granulocyte casts (G) are forming within some dilated tubules (T). cast, cells deposite  Chronic interstitial nephritis chronic not acute CIN is characterised by renal dysfunction with fibrosis and infiltration of the renal parenchyma by lymphocytes, plasma cells and macrophages, in association with tubular damage. Most patients with CIN present in adult life with CKD, HBP and small kidneys. Urinalysis abnormalities are non-specific. Some Px have an impairment of urine-concentrating ability and sodium conservation, which puts them at risk of AKI due to salt and water depletion during an acute illness. Renal tubular acidosis may complicate CIN but is seen most often in myeloma, sarcoidosis, cystinosis, amyloidosis and Sjögren’s syndrome. dry mucosa (autoimmune mediate d) Adult polycystic kidney disease Chronic kidney disease (CKD)  Chronic kidney disease (CKD) acute moree than 3 mth = chronic Refers to an irreversible deterioration in renal function that usually develops over years. Initially, it manifests only as a biochemical abnormality but, eventually, loss of the excretory, metabolic, and endocrine functions of the kidney leads to the clinical symptoms and signs of renal failure, collectively referred to as uremia. When death is likely without RRT (CKD grade 5), it is called end-stage renal no kidney fct : dialisis / disease (ESRD). hormone : EPO, renin, vit D, balance AC/B transplantation Chronic kidney disease (CKD) !! attention the patient is 1 m = not chronic prob !! Crecimiento previsto de las ocho principales causas de muerte en España entre 2016 y 2100 http://www.nephrologyworldwide.com Approach to care for patients with CKD Mortalidad en ERC vs Población general Foley, R., et al. Am J Kidney Dis. (1998).32(5 Suppl.3): S112–S119 The progress of CKD Prevención temprana o tardía y evolución de ERC Diálisis Gansevoort, RT and de Jong, P. J Am Soc Nephrol. 2009 Eventos adversos según albuminuria patient = 1000 = bad -> 15 Gansevoort, RT and de Jong, P. J Am Soc Nephrol. 2009 Biomarcadores if kidney decline fct = vit D supplement = no effect early parameter dead before Calcificación Vascular en ERC compensation of hypoklcemia : PTH = calcium phosphate into circulation Atherosclerosis : entering of CA P = media calcification = imbalance of inhibitor or promotor Bover, J..D'Marco, L. et al. Frontiers Med. 2021  Calcificación Vascular: Intima vs Media Intima Media Aterosclerosis Arteriosclerosis Histología Diffuse punctate morphology. Aggregates of Linear deposits along elastic lamellae. At most severe, a calcium crystals dense circumferential sheet of calcium crystals Consecuencia Obstruccion aguda (oclusiva) Rigidez Vascular (no-oclusiva) CKD, diabetes, aging Occurrence Enf. Cardiovascular (Monckeberg’s sclerosis) Factores Lipid, macrophages, VSMC, inflammation Elastin, VSMC CKD Patients Often Exhibit Both Intimal and Medial Calcification Proudfoot, D. et al. Herz. 2001;26:245-251. Giachelli, C. J Am Soc Nephrol. 2004;15:2959-2964. London, G. et al. Nephrol Dial Transplant. 2003;18:1731-1740. Persy, V. et al. Aterioscler Thromb Vasc Biol. 2006;26:2110-2116 Calcificación de Arterias Coronarias en ERC Aterosclerosis Arteriopatía Urémica Persy, V. et al. Aterioscler Thromb Vasc Biol. 2006;26:2110-2116 Calcifilaxis  METODOS DIAGNOSTICOS No invasivos Rx Simple Ecografía Tomografía – Angio TAC Perfusión Miocárdica Resonancia Karohl, C., D’Marco, L. et al. Nat. Rev. Nephrol. 7, 567–577 (2011) Raggi, P., D’Marco, L. Oxford Textbook of Clinical Nephrology (2015)  METODOS DIAGNOSTICOS Invasivos Angiografía Ultrasonido IV Angioscopia Funcionales Tonometría Karohl, C., D’Marco, L. et al. Nat. Rev. Nephrol. 7, 567–577 (2011) Raggi, P., D’Marco, L. Oxford Textbook of Clinical Nephrology (2015) Physical signs in advanced CKD Suggested investigations in chronic kidney disease anemia , higher ccreatinine , ph acidosis , bicarbonate low , low albumine (proteinuria) , glucose (normal or high), K higher, P hiher or normal  Management hypertension The aims of management in CKD are to: Monitor renal function. Prevent or slow further renal damage. Limit complications of renal failure. Treat risk factors for cardiovascular disease. Prepare for RRT, if appropriate. End-stage renal disease pathway all diabetes and hypertension = chronic kidney disease patient 1.conservative treatment = no dialysis no transplant 2.hemo dialisis 3.peritoneal dialysis 4.transplantation  LAST YEAR Indications for dialysis with examples for AKI and CKD Options for renal replacement therapy UREA potassium = out bicarbonate = in Haemodialysis access Haemodialysis Options for renal replacement therapy bicarbonate in urine potassium = take it out left the original kiney put a new one