4-5

fatty urine cast

"Maltese cross" Nephrotic syndrome

mechanism of Hemorrhagic diathesis in CRF

(platelet function alteration)

ANCA Associated RPGN: CAUSE

- Idiopathic MPA Wegener's

Criteria for RPGN

- May have mild to moderate proteinuria hematuria microscopic glomerular hematuria RBC casts oligo/anuria urinary output <0.3ml/kg/h for or anuria for 12 hours

What are 2 ways to differentiate PSGN from IgA nephropathy?

-complement will be depleted in PSGN -PSGN is later onset after infection

12 A 7‐year‐old boy has become less active over the past 10 days. On physical examination, the boy has facial puffiness. Urinalysis shows no blood, glucose, or ketones, and microscopic examination shows no casts or crystals. The serum creatinine level is normal. A 24‐hour urine collection yields 3.8 g of protein. He improves after corticosteroid therapy. He has two more episodes of proteinuria over the next 4 years, both of which respond to corticosteroid therapy. What is the most likely mechanism causing his disease? A Cytokine‐mediated visceral epithelial cell injury B Cytotoxic T cell-mediated tubular epithelial cell injury C IgA‐mediated mesangial cell injury D Immune complex-mediated glomerular injury E Verocytotoxin‐induced endothelial cell injury

12 A Steroid‐responsive proteinuria in a child is typical of minimal change disease, in which the kidney looks normal by light microscopy, but fusion of foot processes is visible with electron microscopy. The most likely cause of foot process fusion is a primary injury to visceral epithelial cells caused by T cell-derived cytokines. Acute cellular renal transplant rejection is mediated by T cell injury with tubulitis. IgA nephropathy with mesangial IgA deposition and consequent glomerular injury causes recurrent gross or microscopic hematuria and, far less commonly, nephrotic syndrome. Immune complex deposition in membranous nephropathy can cause nephrotic syndrome, but is less common in children than in adults and is not steroid responsive. Certain verocytotoxin‐producing Escherichia coli strains can cause hemolytic uremic syndrome by injury to capillary endothelium.

15 A 12‐year‐old girl has experienced increasing malaise for the past 2 weeks. On physical examination, she has periorbital edema. The child is afebrile. Laboratory findings show proteinuria on dipstick urinalysis, but no hematuria or glucosuria. Microscopic examination of the urine shows numerous oval fat bodies. The serum creatinine level is 2.3 mg/dL. She receives a course of corticosteroid therapy, but does not improve. A renal biopsy is performed and microscopic examination shows that approximately 50% of the glomeruli in the specimen are affected by the lesion shown in the figure. What is the most likely diagnosis? A Dense deposit disease B Focal segmental glomerulosclerosis C Minimal change disease D Nodular glomerulosclerosis E Postinfectious glomerulonephritis F Rapidly progressive glomerulonephritis

15 B Focal segmental glomerulosclerosis (FSGS) shows sclerosis of only a segment of the glomerulus (segmental lesion), and because only 50% of the glomeruli are affected, this is focal disease. FSGS manifests clinically with nephrotic syndrome that does not respond to corticosteroid therapy. FSGS can result from many forms of glomerular injury; some may be linked to NPHS gene mutations. In contrast, corticosteroid‐responsive nephrotic syndrome in children is typically caused by minimal change disease (lipoid nephrosis) that is not associated with any glomerular change seen under the light microscope. Membranoproliferative glomerulonephritis (GN) and dense deposit disease are more likely to produce a nephritic syndrome in adults. A diabetic patient with nephrotic syndrome is likely to have nodular glomerulosclerosis or diffuse thickening of the basement membrane. An acute proliferative postinfectious GN has hypercellular glomeruli with neutrophils. A rapidly progressive GN is associated with hematuria, and glomerular crescents are

16 A 46‐year‐old Hispanic man has had increasing malaise with headaches and easy fatigability for the past 3 months. Physical examination reveals his blood pressure is 200/100 mm Hg. There are no palpable abdominal masses and no costovertebral tenderness. Laboratory studies show hemoglobin, 9.5 g/dL; hematocrit, 28.3%; MCV, 92 μm3; creatinine, 4.5 mg/dL; and urea nitrogen, 42 mg/dL. Urinalysis reveals 3+ hematuria and 3+ proteinuria, but no glucose or leukocytes. A renal biopsy is done; light microscopic examination of the biopsy specimen shows that approximately 50% of the glomeruli appear normal, but the rest show that a portion of the capillary tuft is sclerotic. Immunofluorescence staining shows IgM and C3 deposition in these sclerotic areas. His history is significant for repeated episodes of passing dark brown urine, which failed to respond to corticosteroid therapy. Which of the following mechanisms is most likely responsible for his disease? A Attachment of anti-glomerular basement membrane antibodies B Deposition of immune complexes containing microbial antigens C Deposition of C3 nephritic factor (C3NeF) D Dysfunction of the podocyte slit diaphragm apparatus E Inherited defect in the basement membrane collagen

16 D Corticosteroid‐resistant hematuria and proteinuria leading to hypertension and renal failure is typical for focal segmental glomerulosclerosis (FSGS). FSGS is now the most common cause of nephrotic syndrome in adults in the United States. Specialized extracellular areas overlying the glomerular basement membrane between adjacent foot processes of podocytes are called slit diaphragms, and these exert control over glomerular permeability. Mutations in genes affecting several proteins, including nephrin and podocin, have been found in inherited cases of FSGS; podocyte dysfunction, possibly caused by cytokines or unknown toxic factors, may be responsible for acquired cases of FSGS. FSGS with collapsing glomerulopathy is seen in patients with HIV‐associated nephropathy. Immune complexes containing microbial antigens cause postinfectious glomerulonephritis (GN). Anti-glomerular basement membrane antibodies are responsible for Goodpasture syndrome. C3NeF is an autoantibody directed against C3 convertase, and it is seen in membranoproliferative GN. Inherited defects in basement membrane collagen cause Alport syndrome, also characterized by hematuria, but other congenital abnormalities, such as deafness, are often present, and

17 A 38‐year‐old woman has been feeling lethargic for 4 months. On physical examination, she is afebrile, and her blood pressure is 140/90 mm Hg. Laboratory findings show the serum creatinine level is 5.8 mg/dL. C3 nephritic factor is present in serum, resulting in hypocomplementemia, and the ANA test result is negative. Urinalysis shows 2+ blood and 1+ protein. A renal biopsy is done; microscopic examination shows hypercellular glomeruli and prominent ribbonlike deposits along the lamina densa of the glomerular basement membrane. Which of the following forms of glomerulonephritis is most likely to be present in this patient? A Chronic glomerulonephritis B Dense deposit disease C Membranous nephropathy D Postinfectious glomerulonephritis E Rapidly progressive glomerulonephritis

17 B Dense deposit disease (formerly membranoproliferative glomerulonephritis type II) usually leads to hematuria, and half of cases end in chronic renal failure. The term chronic glomerulonephritis (GN) often is used when sclerosis of many glomeruli is present with no clear cause. Membranous nephropathy is often accompanied by proteinuria but less likely hematuria, and is characterized by thickening of only the basement membrane and small electron‐dense deposits. Postinfectious GN is often characterized by a hypercellular glomerulus with infiltration of polymorphonuclear leukocytes, but no basement membrane thickening. A rapidly progressive GN is marked by crescents forming in the Bowman space.

23 A 33‐year‐old woman has had fever and increasing fatigue for the past 2 months. Over the past year, she has noticed soreness of her muscles and joints and has had a 4‐kg weight loss. On physical examination, her temperature is 37.5° C, pulse is 80/min, respirations are 15/min, and blood pressure is 145/95 mm Hg. She has pain on deep inspiration, and a friction rub is heard on auscultation of the chest. Laboratory findings show glucose, 73 mg/dL; total protein, 5.2 g/dL; albumin, 2.9 g/dL; and creatinine, 2.4 mg/dL. Serum complement levels are decreased. CBC shows hemoglobin of 9.7 g船/dL, platelet count of 85,000/mm3, and WBC count of 3560/mm3. A renal biopsy specimen shows a diffuse proliferative glomerulonephritis with extensive granular immune deposits of IgG and C1q in capillary loops and mesangium. After being treated with immunosuppressive therapy consisting of prednisone and cyclophosphamide, her condition improves. Which of the following serologic studies is most likely to be positive in this patient? A Anticentromere antibody B Anti-DNA topoisomerase I antibody C Anti-double‐stranded DNA antibody D Anti-glomerular basement membrane antibody E Antihistone antibody F Antineutrophil cytoplasmic autoantibody G Antiribonucleoprotein

23 D The pulmonary function data suggest a restrictive lung disease process. The progressive pulmonary interstitial fibrosis of a restrictive lung disease such as a pneumoconiosis can eventually lead to dilation of remaining residual proximal airspaces, giving a honeycomb appearance. The loss of lung tissue with emphysema also leads to airspace dilation, but without alveolar wall fibrogenesis. Eosinophilic infiltrates suggest atopic asthma, an episodic disease without fibrogenesis. The increase in mucous glands with chronic bronchitis leads to copious sputum production, but not fibrogenesis. Hyaline membranes, edema, inflammation, and focal necrosis are features of diffuse alveolar damage (acute respiratory distress syndrome) in the acute phase; if patients survive for weeks, diffuse alveolar damage may resolve to honeycomb change.

24 A 33‐year‐old woman with a history of intravenous drug use comes to the emergency department because she has had a high fever for the past 2 days. On physical examination, her temperature is 38.4° C. She has a palpable spleen tip, bilateral costovertebral angle tenderness, and diastolic cardiac murmur. Laboratory findings show a serum urea nitrogen level of 15 mg/dL. Urinalysis shows 2+ hematuria, and no glucose, protein, or ketones. A blood culture is positive for Staphylococcus aureus. Which of the following best describes the likely gross appearance of the kidneys in this patient? A Enlarged, and replaced by 1‐ to 4‐cm, fluid‐filled cysts B Marked pelvic and calyceal dilation with thinning of the cortices C Normal size, with smooth cortical surfaces D Shrunken, with uniformly finely granular cortical surfaces E Slightly swollen, with scattered petechial hemorrhages F Small and asymmetric, with irregular cortical scars and marked calyceal dilation G Wedge‐shaped regions of yellow‐white cortical necrosis

24 G This patient is septic, and the heart murmur strongly suggests infective endocarditis. Cardiac lesions are the source of emboli (from valvular vegetations or mural thrombi) that can lodge in renal artery branches, producing areas of coagulative necrosis. These areas of acute infarction typically are wedge‐shaped on cut section because of the vascular flow pattern. In addition, these septic emboli can produce abscesses where they lodge in the vasculature. Bilaterally enlarged, cystic kidneys are typical of autosomal dominant polycystic kidney disease. This patient's kidneys may have been normal‐sized and smooth‐surfaced before this event. Small, shrunken kidneys represent an end stage of many chronic renal diseases. Petechiae and edema may be seen in hyperplastic arteriolosclerosis associated with malignant hypertension. Irregular cortical scars with pelvicalyceal dilation may represent hydronephrosis complicated by infection in chronic pyelonephritis, whereas dilation alone points to obstructive uropathy, such as occurs with bladder outlet obstruction.

26 A 58‐year‐old man is found to have mild hypertension. Laboratory findings show a serum creatinine level of 2.2 mg/dL and urea nitrogen level of 25 mg/dL. Microalbuminuria is present, with excretion of 250 mg/day of albumin. Two years later, he remains hypertensive and has a serum creatinine level of 3.8 mg/dL, urea nitrogen level of 38 mg/dL, and 24‐hour urine protein level of 2.8 g. A renal biopsy shows discrete mesangial lesions. Blood/serum test for which of the following is most likely to be abnormal in this patient? A Anti-glomerular basement membrane antibody B Antinuclear antibody C Anti-neutrophil cytoplasmic autoantibody D Anti-streptolysin O E C3 nephritic factor F Hemoglobin A1c G Hepatitis B surface antigen

26 F The figure shows nodular and diffuse glomerulosclerosis that often occur in patients with long‐standing diabetes mellitus, which is often complicated by urinary tract infections. Infections with bacterial organisms also occur more frequently in patients with diabetes mellitus who have an elevated Hgb A1c. Deposits of IgG and C3 in the glomerular basement membrane occur with forms of glomerulonephritis (GN) caused by immune complex deposition, including lupus nephritis and membranous nephropathy. The only abnormality observed in minimal change disease is effacement of podocyte foot processes, but this change is not specific for minimal change disease and may be seen in other disorders that produce proteinuria. Crescentic GN is not typically seen in diabetes mellitus. IgA deposition in the mesangium occurs in IgA nephropathy (Berger disease). A necrotizing granulomatous vasculitis can be present in the kidneys of patients having granulomatosis with polyangiitis (ANCA‐associated vasculitis).

3 A 29‐year‐old man with chronic hepatitis C virus infection has noted dark urine for the past 2 weeks. On examination he is hypertensive but afebrile. Laboratory studies show serum creatinine of 3.8 mg/dL and urea nitrogen of 35 mg/dL. Cryoglobulins are detected. Urinalysis shows RBCs and RBC casts. A renal biopsy is performed and microscopically shows hypercellular glomeruli with lobulation and a double‐ contour appearance to split basement membranes adjacent to subendothelial immune complexes. Which of the following cell types has most likely proliferated in his glomeruli? A Juxtaglomerular cells B Mesangial cells C Parietal epithelial cells D Podocytes E Endothelial cells

3 B The appearance of membranoproliferative glomerulonephritis, a cause for nephritic syndrome in adults, is described. Mesangial cells have a phagocytic function, but they also can elaborate inflammatory mediators, cytokines, and matrix. Proliferation of mesangial cells may be induced by injury, particularly immune complex deposition. Juxtaglomerular cells secrete renin. Parietal epithelial cells line the Bowman capsule and may proliferate with severe glomerular injury to produce crescents. Podocytes are visceral epithelial cells that form the filtration barrier. Endothelial cells are most likely to be damaged with thrombotic microangiopathies.

normal pH of urine

6

6 A 17‐year‐old girl living in the Congo has had a chronic febrile illness for 2 years. In the past 2 days she notes her urine is smoky brown. On physical examination her blood pressure is 145/95 mm Hg. Laboratory studies show her serum creatinine is 3.7 mg/dL, and urea nitrogen is 35 mg/dL. Urinalysis shows 4+ blood with 1+ protein, but no glucose, ketones, or leukocytes. The serum haptoglobin is decreased and Coombs test is negative. Her Hgb is 8.5 g/dL. A peripheral blood smear shows rare ring stage trophozoites. Immunofluorescence microscopy performed on renal biopsy shows granular deposition of IgG and C3 in glomerular capillary basement membranes. Electron microscopy shows electron‐dense subepithelial "humps." Which of the following renal diseases is she most likely to have? A Focal segmental glomerulosclerosis B Hereditary nephritis C IgA nephropathy D Lupus nephritis E Membranous nephropathy F Acute proliferative glomerulonephritis

6 F She has Plasmodium infection with malaria and immune complex deposition with leukocytes in glomeruli that has led to a nephritic syndrome associated with her acute proliferative glomerulonephritis; many of these are post‐infectious. The inciting infection depends upon the locale and frequency of occurrence. In the United States, Staphylococcus aureus (with IgA antibodies) is now more common than Streptococcus pyogenes as a cause for postinfectious GN in developed nations. Of the remaining choices, only membranous GN is likely to have an infectious cause, but this is more likely to produce a nephrotic syndrome.

8 A 21‐year‐old previously healthy man has noticed blood in his urine for the past 2 days. He reports no dysuria, frequency, or hesitancy of urination. On physical examination, there are no abnormal findings. Laboratory findings show a serum urea nitrogen level of 39 mg/dL and creatinine level of 4.1 mg/dL. A renal biopsy specimen is obtained; the immunofluorescence pattern of staining with antibody against human IgG is shown in the figure. Which of the following serologic findings is most likely to be present in this patient? A Anti-glomerular basement membrane antibody B Anti-streptolysin O antibody C C3 nephritic factor D Hepatitis B surface antibody E HIV antibody

8 A The linear pattern of staining shown in the figure indicates the presence of anti-glomerular basement membrane antibodies (directed against the noncollagenous domain of the α3 chain of type IV collagen). Such antibodies are typically seen in Goodpasture syndrome, a form of rapidly progressive glomerulonephritis (GN) that has a bimodal pattern of occurrence in younger and older men. The anti-streptolysin O titer is increased in poststreptococcal GN, which typically has a granular pattern of immune complex deposition. The C3 nephritic factor can be a marker for dense deposit disease. Some cases of membranous nephropathy are associated with hepatitis B virus infection, but the immune complex deposition is granular, not linear. HIV infection can lead to a nephropathy that resembles FSGS, in which IgM and C3 are deposited in the mesangial areas of affected glomeruli.

9 A 46‐year‐old woman has had worsening malaise for the past 36 hours. Her urine output is markedly diminished, and it has a cloudy brown appearance. On examination she has periorbital edema. Laboratory findings include serum creatinine of 2.8 mg/dL and urea nitrogen of 30 mg/dL. A renal biopsy is performed and on microscopic examination shows focal necrosis in glomeruli with glomerular basement membrane breaks and crescent formation. No immune deposits are identified with immunofluorescence. Which of the following autoantibodies is most likely detectable in her serum? A Anti-DNA topoisomerase antibody B Anti-glomerular basement membrane antibody C Anti-neutrophil cytoplasmic autoantibody D Antinuclear antibody E Anti‐HBs Ag

9 C This is pauci‐immune crescentic glomerulonephritis. The lack of immune deposits excludes anti-glomerular basement membrane disease (Goodpasture syndrome). Cases can be idiopathic, associated with ANCAs, and limited to the kidney. Rapidly progressive GN often has an abrupt onset with nephritis marked by oliguria. Anti-DNA topoisomerase antibody is seen with scleroderma, which mainly affects the vasculature. Antinuclear antibody is present with many autoimmune diseases, such as SLE, with immune complex deposition in glomeruli. Anti‐HBs may occur in some cases of secondary membranous nephropathy.

anuria

<100 mL/d

End -stage renal disease (ESRD) GFR

<20 ml

oliguria

<400 mL/d

polyuria

>3.0 L/d

dirty brown granular casts

ATN

• Markedly reduced urine flow (oliguria) or no renal flow (anuria) • Recent onset azotemia

Acute Renal Failure

Do WBC casts indicate acute pyelonephritis or cystitis?

Acute pyelonephritis

broad urine cast

As usual waxy cast, but 2 3 times wider - = Renal failure casts (CRF: tubular atrophy and dilation)

elevated Blood urea nitrogen and creatinine levels --due to reduced glomerular filtration rate (GFR)

Azotemia

7 A 45‐year‐old man has experienced increasing malaise, nausea, and reduced urine output for the past 3 days. On physical examination, he is afebrile and normotensive. Laboratory findings show a serum creatinine level of 7.5 mg/dL. Urinalysis shows hematuria, but no pyuria or glucosuria. A renal biopsy is done; the light microscopic picture is shown in the figure. Which of the following additional studies is most useful for classification and treatment of this disease? A Antinuclear antibody B Anti-glomerular basement membrane antibody C HIV‐1 RNA copy level D Quantitative serum immunoglobulins E Rheumatoid factor F Urine immunoelectrophoresis

B

Yellow/green urine

Bile pigments: Bilirubin Obstructive Jaundice

granular urine cast

Breakdown of cellular (RBC/WBC/ renal tubular) cast Acute tubular necrosis Pyelonephritis Drug - induced interstitial nephritis

most common pre-Renal causes of ARF

Burns Conditions that allow fluid to escape from the bloodstream Loss of blood volume (such as with dehydration) Prolonged vomiting or diarrhea, Bleeding Reduced Stroke Volume Heart Failure Shock Renal Blood Flow Obstruction - Certain types of surgery Renal Artery Embolism Renal Artery Occlusion Trauma to the kidney

21 A 56‐year‐old woman is found on health screening to have a blood pressure of 168/109 mm Hg. No other physical examination findings are noted. Urinalysis shows a pH of 7.0; specific gravity, 1.020; 1+ proteinuria; and no blood, glucose, or ketones. The ANA and ANCA test results are negative. The serum urea nitrogen level is 51 mg/dL, and the creatinine level is 4.7 mg/dL. The hemoglobin A1c concentration is within the reference range. An abdominal ultrasound scan shows bilaterally and symmetrically small kidneys with no masses. What is her most likely diagnosis? A Amyloidosis B Autosomal dominant polycystic kidney disease C Chronic glomerulonephritis D Microscopic polyangiitis E Nodular glomerulosclerosis

C Chronic glomerulonephritis (GN) may follow specific forms of acute GN. In many cases, however, it develops insidiously with no known cause. With progressive glomerular injury and sclerosis, both kidneys become smaller, and their surfaces become granular. Hypertension often develops because of renal ischemia. Regardless of the initiating cause, these "end‐stage" kidneys appear morphologically identical. They have sclerotic glomeruli, thickened arteries, and chronic inflammation of interstitium. Because the patient's ANA and ANCA test results are negative, vasculitis is unlikely. Polycystic kidney disease and amyloidosis would cause the kidney size to increase, not decrease. The normal hemoglobin A1c concentration indicates that the patient does not have diabetes mellitus. Nodular glomerulosclerosis is typical of diabetes mellitus with an elevated hemoglobin A1c.

Complications of CRF

CHF, Htn, osteomalacia, osteitis fibrosa cystica, normocytic anemia (erythropoietin) Uremia

Prolonged uremia (> 3 months, usually years)

CRF

Cloudy urine

Crystals, cells, others, Urolithiasis, Infection

where are RBC casts usually found?

DCT

Red/brown urine

Dysmorphic RBCs and Casts, Methemoglobin Glomerulonephritis, Muscle injury, Unstable Hb

often a sign of glomerular disease and originate in the renal DCT and RBCs from any point along the urinary tract.

Dysmorphic RBCs are

4 A study of renal disease identifies patients with greater than 3.5 g of protein in a 24‐hour urine collection, but no RBCs or WBCs. Dysfunction involving which of the following cells is most likely to be responsible for proteinuria? A Endothelium B Macula densa C Mesangium D Parietal epithelium E Podocytes

E The podocytes (visceral epithelial cells) of the glomerulus form a filtration barrier that depends upon both the anionic charge as well as slit diaphragms. Injuries that cause effacement, retraction, detachment, and vacuolization allow protein, principally albumin, to escape into Bowman space. Podocytes have limited capacity for regeneration and repair. The loss of 3.5 g/day of protein defines nephrotic syndrome. About a sixth of filtration occurs through the mesangium. The remaining listed options do not participate in this epithelial protein filtration barrier.

waxy urine cast

From granular casts, with sharp borders CRF, reflect stasis within tubules and oliguria

Clear, proteinaceous urine cast

Hyaline Normal, more in Proteinuria

Name 3 diseases that may cause Isolated Hematuria / Proteinuria.

IgA Nephropathy (Berger's disease) thin basement membrane disease Alport's syndrome

seen in Diabetics, also in cachexia and febrile illness

Ketonuria

Milky urine

Lipids, Chyle, Cells, Nephrosis, filariasis, Infection

How does uremia cause low serum Ca?

Loss of Kidney parenchyma -> decreased hydroxycalciferol activation -> decreased intestinal reabsorption of Ca2+ calciuria

3 Factors that favor protein cast formation are

Low flow rate High salt concentration Low pH All these favor protein denaturation precipitation (esp. Tamm-Horsfall protein)

Brown black urine

Methemoglobin, melanin, Homogentisic acid Rhabdomyolysis, Alkaptonuria

• HEMATURIA (blood in urine) DUE TO GLOMERULAR DISEASE. (blood from glomerular disease shows red cell casts on urinalysis) • Abnormal renal function • Usually have azotemia, oliguria and hypertension • Mild proteinuria and edema also common

Nephritic syndrome

proteinuria (> 3.5 grams per day) • Hypoabuminemia • Severe edema • Hyperlipidemia • Lipiduria (lipid in urine/fatty casts)

Nephrotic Syndrome

BUN:Cr Ratio 10:1

Normal range. Normal, post,-renal, orRenal Disease Both BUN and creatinine are not excreted, therefore both are high but the ratio is maintained.

13 A 44‐year‐old man with increasing malaise for the past month now is bothered by increasing swelling in the hands and legs. On physical examination, there is generalized edema. He is afebrile, and his blood pressure is 140/90 mm Hg. Urinalysis shows a pH of 6.5; specific gravity 1.017; 4+ proteinuria; and no blood, glucose, or ketones. Microscopic examination of the urine shows no casts or RBCs and 2 WBCs per high‐power field. The 24‐hour urine protein level is 4.2 g. A renal biopsy specimen is obtained, and immunofluorescence staining with antibody to the C3 component of complement produces the pattern shown in the figure. Which of the following underlying disease processes is most likely to be present in this man? A Chronic hepatitis B virus infection B HIV infection C Multiple myeloma D Recurrent urinary tract infection E Nephrolithiasis

One of the most common causes of nephrotic syndrome in adults is membranous nephropathy, caused by immune complex deposition, shown in the figure as extensive granular deposits with C3. About 75% of cases are idiopathic and due to autoantibodies reacting against podocyte antigens; but some cases follow infections (e.g., hepatitis, malaria), or are associated with causes such as malignancies or autoimmune diseases. In some cases of AIDS, a nephropathy resembling focal segmental glomerulosclerosis occurs. Multiple myeloma can be complicated by systemic amyloidosis, which can involve the kidney. Recurrent urinary tract infections are typically caused by bacterial organisms and can cause chronic pyelonephritis. Nephrolithiasis may lead to interstitial nephritis, but it does not cause glomerular injury.

(Acute) Nephritic Syndrome: Causes

PSGN (RPGN) Acute proliferative GN (APGN) or Post infective GN Many, but not all cases Membrano-proliferative GN (MPGN) Including SLE associated MPGN

causes of non glomerular hematuria

Polycystic kidneys (+ hypertension and flank pain) Renal and Bladder cancer (+ a mass) Urolithiasis or Renal infarction (+ flank pain and renal colic) Acute Cystitis (+ frequency and dysuria), etc

BUN:Cr Ratio >20:1

Pre- Renal ARF - Reduced flow, elevated BUN within kidney; Essentially creatinine is not reabsorbed

A Brownish urine cast indicates which syndrome(s)?

RBC Glomerulonephritits , Nephritic syndrome

• Nephritic syndrome with rapid decline in GFR • (Nephritic syndrome + acute renal failure)

Rapidly Progessive Glomerulonephritis

Epithelial urine cast

Tubular epithelium Acute tubular necrosis

Azotemia + other biochemical abnormalities + clinical findings

Uremia

Diagnosis of Chronic Renal Failure (CRF)

Uremia (Cr > 4 mg/ - Reduced GFR (< 60 ml/min) : Waxy and Broad casts Metabolic Acidosis, low Ca, retention of sodium, potassium, phosphate

Yellow/orange urine could indicate?

Urobilin, Bilirubin Dehydration, Liver disease, Hemolysis

WBC urine cast

WBC, Neutrophils or Eosinophils SEEN Acute pyelonephritis Drug induced interstitial nephritis

Does uremia cause acidosis or alkalosis?

acidosis

RBCs and RBC casts

acute glomerulonephritis

WBC casts/eosinophils

acute tubulointerstitial nephritis

RPGN: CAUSE

anti-GBM - Idiopathic - Goodpasture syndrome Immune complex - Idiopathic - Post infectious/infection related - SLE - HenochSchonlein purpura/IgA Nephropathy ANCA Associated - Idiopathic MPA Wegener's

Urinary calculi are most commonly formed by

calcium. Work up of the habitual stone formation should include both analysis of the urine and stone

where are hyaline casts usually found?

collecting duct

mechanism of normocytic anemia in chronic kidney injury

decreased erythropoietin

top causes of CRF

diabetes, hypertension, Glomerulonephritis, Polycystic Kidney Disease, Chronic Urinary Tract Infections, Nephrolithiasis, Vasculitis

used to diagnose urinary tract leucocyte infections. Positive results should be verified by microscopy and culture

dipstick nitrite and esterase

10 A 44‐year‐old woman has developed a fever, nonproductive cough, and decreased urine output over the past 3 days. On physical examination, her temperature is 37.7° C, and blood pressure is 145/95 mm Hg. She has sinusitis. On auscultation, crackles are heard over all lung fields. A chest radiograph shows bilateral patchy infiltrates and nodules. The serum creatinine level is 4.1 mg/dL, and the urea nitrogen level is 43 mg/dL. The results of serologic testing are negative for ANA, but positive for C‐ANCA. A renal biopsy specimen shows glomerular crescents and damage to small arteries. The result of immunofluorescence staining with anti‐IgG and anti‐C3 antibodies is negative. Which of the following additional microscopic findings is most likely to be seen in this biopsy? A Focal segmental glomerulosclerosis B Glomerular basement membrane thickening C Hyperplastic arteriolosclerosis D Infiltrations by neutrophils E Mesangial proliferation F Necrotizing granulomatous vasculitis

glomerulonephritis (GN) characterized by epithelial crescents in Bowman space. Several features differentiate it from other forms of crescentic GN (e.g., Goodpasture syndrome), including the presence of granulomatous vasculitis, the absence of immune complexes or anti-glomerular basement membrane (GBM) antibodies, and the presence of C‐ANCA. Focal segmental glomerulosclerosis (FSGS) does not affect renal vessels and is unlikely to produce crescents with a rapidly progressive presentation. Goodpasture syndrome is a form of rapidly progressive GN with crescent formation, but a granulomatous vasculitis is not present, and there is anti‐GBM antibody, not C‐ANCA. Hyperplastic arteriolosclerosis can lead to focal hemorrhages and necrosis, but without a granulomatous component, and the blood pressure is usually quite high. Lupus nephritis, membranoproliferative GN, and postinfectious GN (with many neutrophils in glomeruli) occasionally can have a rapidly progressive course with crescent formation, but they do not produce granulomatous vasculitis. In patients with lupus, the ANA test result is often positive. Membranous nephropathy is most likely to produce nephrotic syndrome without crescents.

direct damage to kidneys by inflammation, toxins, infection, or reduced blood supply

intrarenal failure

urine color: red : "Fresh" (Normal) RBCs, no RBC casts

non glomerular hematuria

Urinary out flow obstruction

postrenal failure

sudden obstruction of urine flow due to a mass or injury

postrenal failure

A drop in bp or interruption of rbf causes what kind of renal failure?

prerenal failure

Alkaline, NH 4 smell urine

proteus infection

effects of uremia on K+, Po4, sodium, water

retained

Systemic Manifestations of Uremia

• Dehydration,Edema, • Hyperphosphatemia Hyperkalemia Hypocalcemia • Anemia ,Bleeding diathesis • Sallowcolor • Myopathy, Metabolic acidosis, Secondary hyperparathyroidism, Renal osteodystrophy • Hypertension, CHF, Pulmonary edema, Uremic pericarditis , Gastritis, colitis, • Nausea, vomitting , GI bleeds, esophagitis, Pruritis , Peripheral neuropathy, Encephalopathy

Causes of Azotemia

• Prerenal - from reduced blood flow to kidneys • Renal - kidney disease • Post renal - obstruction of urine flow