Acute renal failure, chronic renal failure - Pathology - ATOT

Topic: Acute renal failure, chronic renal failure
Faculty: Pathology - Medical
Course: ATOT 2nd year

- Acute renal failure: definition, causes, pathogenesis, morphology, clinical course, diagnosis, treatment
- Chronic renal failure: definition, causes, pathogenesis, stages, clinical features, diagnosis, treatment
- Renal system - charts

1. ARF, CRF Dr. Salman Ansari MBBS 07/03/23

2. ARF CRF Charts

3. ACUTE RENAL FAILURE New name: AKI

4. ARF Definition Causes Pathogenesis Morphology Stages Clinical features Diagnosis , treatment

5. Acute Renal Failure(ARF) Definition : rapid reduction of renal function, with severe oliguria Now known as AKI(acute kidney injury) ATI is the most common cause of acute kidney injury(acute renal failure) ATI →AKI/ARF

6. Commonly seen in hospital setting Very common in ICU patients

7. KDIGO criteria According to KDIGO(Kidney Disease: Improving Global Outcomes), AKI is the presence of any of the following: Increase in serum creatinine by 0.3 mg/dL or more (26.5 micromoles/L or more) within 48 hours Increase in serum creatinine to 1.5 times or more baseline within the prior seven days Urine volume less than 0.5 mL/kg/h for at least 6 hours

8. Causes of AKI Divided into 3 categories Pre-renal (60%) R enal (35%) Post-renal (5%)

9. Pre-renal Any cause that reduces blood flow to kidney Fluid loss: due to blood loss, burns, diarrhoea, vomiting Hypotension: shock, pulmonary embolism Medications which cause renal vasoconstriction: NSAIDs, ACEI, ARBs, iodinated contrast, metformin

10. 2. Renal Any condition which affects the tubules or glomeruli of kidney Acute tubular necrosis(ATN) Acute glomerulonephritis(AGN) Medications which cause acute interstitial nephritis(AIN): clavulanic acid, penicillins, NSAIDs

11. 3. Post-renal Any obstruction to urine flow Renal stones Blocked catheter tumours BPH(benign prostatic hyperplasia) in older men

12. Pre-renal Renal Post-renal Fluid loss: bleeding, burns diarrhoea, vomiting Acute tubular necrosis(ATN) Renal calculi Hypotension: shock Acute glomerulonephritis(AGN) Blocked catheter Drugs: NSAIDs Diuretics Contrast dye ACEI/ARB Metformin Acute interstitial nephritis(AIN) due to drugs like: NSAIDs Penicillins Clavulanic acid BPH Tumours

13. Injury to tubular epithelial cells, due to ischemia/toxins ↓ Leads to back-leakage of fluid from lumen into interstitium ↓ Damaged tubular epithelial cells detach and form casts , which blocks the lumen ↓ Luminal obstruction leads to: (1)increased tubular pressure, (2) decreased GFR and (3) decreased urine flow ↓ Ischemia also causes vasoconstriction which reduces GFR and oxygen supply to tubules ↓ Acute tubular injury Pathogenesis of AKI → Acute kidney injury

14. Morphology Gross Both kidneys are swollen with a pale cortex and congested medulla Microscopy Glomeruli: normal Tubules: focal and multiple areas of damage, most prominently in proximal tubules and ascending limb of loop of Henle Interstitium: edema, leukocytes Blood vessels: normal Ischemic kidney injury

15. Toxic kidney injury Microscopy: Proximal convoluted tubule(PCT) is affected most commonly More necrosis is seen as compared to ischemic ATN Toxic kidney injury

16. Clinical course 3 stages: Initiation phase Maintenance phase Recovery phase Mild ↓urine output, ↑ in BUN ↓↓ in urine output(oliguria), salt and water overload, rising BUN, hyperkalemia, metabolic acidosis and other features of uremia Steady ↑ in urine volume Loss of large amounts of water, Na and K in urine(leads of hypokalemia)

17. Clinical course 3 stages: Initiation phase Maintenance phase Recovery phase Mild ↓urine output, ↑ in BUN ↓↓ in urine output(oliguria), salt and water overload, rising BUN, hyperkalemia, metabolic acidosis and other features of uremia Steady ↑ in urine volume Loss of large amounts of water, Na and K in urine(leads of hypokalemia)

18. Clinical features Decreased or no urine output Edema Nausea Weight gain Shortness of breath Hypertension Confusion

19. Diagnosis ↓ urine volume RFT: S. urea, S.creat ↑ hyperkalemia eGFR: 🙅 not useful in AKI 🙅

20. Treatment AKI is often reversible Treatment depends upon the cause(pre/renal/post) Maintain BP and urine output If hypovolemic: give IV fluids I/O monitoring Hyperkalemia: treated by dietary restriction or medications(insulin) Stop any nephrotoxic drugs ( Mnemonic :“stop the DAMN” drugs) If obstruction suspected: do USG abdomen and pelvis Dialysis D - Diuretics A - ACEI/ARB M - Metformin N - NSAIDs

21. CHRONIC RENAL FAILURE

22. CRF Definition Causes Pathogenesis Stages of CRF Clinical features Diagnosis , treatment

23. Chronic renal failure Definition : gradual and irreversible decline in renal function due to slow destruction of renal tissue Kidneys will be shrunken GFR less than 50% or <60 ml/min, for 3 months or more

24. Etiology 1, Diseases affecting glomerulus : Chronic glomerulonephritis diabetic nephropathy 2. Diseases affecting tubules and interstitium : Vascular: long-standing hypertension Infectious: chronic pyelonephritis Toxic: long-term use of nephrotoxic drugs(aspirin, paracetamol), lead Obstruction: tumours, kidney stones

25. Pathogenesis Damage to glomerulus leads to changes in filtration, and development of nephrotic syndrome(proteinuria, hypoalbuminemia and oedema) Damage to tubules leads to changes in reabsorption and secretion of important substances, leading to excretion in large amounts of dilute urine

26. Stages of CRF 5 stages, depending upon the GF R Normal: GFR: 50-100% Decreased renal reserve : GFR is <50% Renal insufficiency : GFR: <25% Renal failure : GFR: <10% End-stage kidney disease : GFR: <5%

27. Clinical features Renal symptoms + extra-renal symptoms Renal symptoms : Metabolic acidosis: Kussmaul breathing(rapid, deep breathing) Hyperkalemia: weakness, nausea, cardiac arrhythmia, diarrhoea Sodium and water imbalance: congestive heart failure Hyperuricemia: uric acid crystals in joints and soft tissues - “gout” Azotaemia: high serum urea, creatinine

28. Non-renal symptoms : Anemia (due to decreased production of erythropoietin) Yellowing of skin Congestive heart failure Pulmonary oedema Renal osteodystrophy

29. Diagnosis of CKD CBC: anemia Hyperkalemia RFT(renal function tests): increased serum urea, serum creatinine eGFR(estimated GFR): reduced to <50% or <60 ml/min USG Abdomen and Pelvis : shrunken kidneys Biopsy may be needed

30. Treatment No cure - treatment can only slow the disease L ifestyle changes, “renal diet”: low salt, protein and phosphorous M aintain BP C ontrol blood sugar in diabetics T reat uremia by: Dialysis : 2 types - hemodialysis and peritoneal dialysis renal transplant Mnemonic : “LMCT” - Let Me Cure This

31. CHART - Renal system - 1 A 56 year old women is diagnosed with diabetes since 25 years. On examination, she has a blood pressure of 168/110 mmHg. Patient appears pale. No other abnormalities identified. Her investigations show: Urinalysis pH: 7.0 Spec. grav: 1.010 Proteinuria: 2+ Urine glucose: Positive Abdominal USG shows bilateral symmetrically small kidneys Blood S. urea nitrogen: 71 mg/dl Creatinine: 4.7 mg/dl Hemoglobin: 9 mg/dl Questions : 1) What is the most likely diagnosis? 2) Why do you say so? 3) What is the other common condition that can progress to this condition? 4) Why is the patient anemic?

32. Questions : 1) What is the most likely diagnosis? 2) Why do you say so? 3) What is the other common condition that can progress to this condition? 4) Why is the patient anemic? Answers : Chronic renal failure Deranged S. urea and creatinine in the presence of shrunken kidneys Long-standing hypertension In CRF, the kidneys are not able to produce enough erythropoietin(EPO), thus there is decreased synthesis of RBCs, leading to anemia.

33. CHART - Renal system - 2 A 54 year old male with a history of coronary artery disease came with complaints of increasing tiredness since last month. He also said that his abdomen was growing larger in size and he had gained 15 kg over the past month. During the past week he has had breathlessness and his feet have swollen. Cardiac echo shows ejection fraction of 30%. On physical examination, the patient is in moderate respiratory distress. BP is 140/80mmHg, pulse 95/min and RR 28/min. Body weight: 91 kg. Abdomen is enlarged with a positive fluid wave. Lower extremities showed pitting oedema.

34. Lab data May July 1 July 2 July 3 Normal Sodium 130 133 134 133 136-146 mmol/L Potassium 4.9 5.7 5.8 6.0 3.5-5.0 mmol/L Chloride 100 90 91 93 102-109 mmol/L BUN 20 87 94 101 7-20 mg/dl Creatinine 0.9 3.0 3.5 3.7 0.6-1.2 mg/dl Renal ultrasound : right kidney 10 x 5.5, left kidney 10.5 x 6.0. Both kidneys demonstrate normal echogenicity and are without masses or cysts. There is no hydronephrosis.

35. Questions : Is the type of kidney injury acute or chronic? Why? What is the cause of kidney injury in this case? Answers : A1) Acute kidney injury Reasons: Symptoms are of short duration(1 month) Sudden rise in urea and creatinine levels in a short span of time Ultrasound shows kidneys of normal echogenicity A2) AKI is because of his heart failure. The ejection fraction is low(30%), which means the heart is not able to pump blood with enough pressure to maintain the GFR. Therefore the kidneys are not able to clear urea and creatinine from the body adequately, leading to rise of blood levels of the same.

36. References: Ramadas Nayak - Textbook of Pathology for Allied Health Sciences StatPearls - Acute kidney injury StatPearls - Chronic renal failure Questions: [email protected] For notes, scan: For PPT, scan: