RR 2024 Renal

Question 1

most frequent cause of nephrotic syndrome in children

Answer 1

Minimal-change disease

Question 2

It is manifested by proteinuria and effacement of glomerular foot processes without antibody deposits.

Answer 2

Minimal-change disease

Question 3

May be primary or secondary (e.g., as a consequence of previous glomerulonephritis, hypertension, or infection such as HIV). Glomeruli show focal and segmental obliteration of capillary lumina and loss of foot processes.

Answer 3

Focal segmental glomerulosclerosis (FSGS)

Question 4

Caused by an autoimmune response, most often directed against the PLA2R on podocytes. It is characterized by granular subepithelial deposits of antibodies with GBM “spike” formation, thickening and loss of foot processes but little or no inflammation.

Answer 4

Membranous nephropathy

Question 5

an immune complex–mediated disease with immune deposits in the subendothelial location.

Answer 5

Membranoproliferative glomerulonephritis type 1

Question 6

Caused by unregulated activation of the alternative complement pathway. Immunofluorescence is positive for C3 in both conditions.

Answer 6

Dense deposit disease and C3 glomerulonephritis

Question 7

Caused by deposition of immune complexes, mainly in the subepithelial spaces, with abundant neutrophils and proliferation of glomerular cells.

Answer 7

Acute postinfectious glomerulonephritis typically occurs after streptococcal infection in children and young adults but may occur following infection with many other organisms.

Question 8

Diseases That Present Mostly With Asymptomatic Hematuria

Answer 8

IgA nephropathy
Hereditary nephritis (Alport syndrome)

Question 9

most common form of glomerulonephritis worldwide

Answer 9

IgA nephropathy

Question 10

Recurrent asymptomatic hematuria is the most common clinical presentation. It commonly affects children and young adults and has a variable course.

Answer 10

IgA nephropathy, characterized by mesangial deposits of IgA-containing immune complexes.

Question 11

an important cause of ascending infection.

Answer 11

Incompetence of the vesicoureteral orifice, resulting in vesicoureteral reflux (VUR)

Question 12

three predisposing conditions for papillary necrosis, a rare form of pyelonephritis,.

Answer 12

diabetes, urinary tract obstruction, and sickle cell anemia

Question 13

Tamm-Horsfall protein

Answer 13

Also known as uromodulin, from UMOD gene on #16
a high molecular weight glycoprotein discovered by Tamm and Horsfall (J Exp Med 1952;95:71)
Normally synthesized by thick ascending limb of loop of Henle, possibly distal convoluted tubules
Most abundant protein in urine of healthy individuals
(normally secreted by tubular epithelium) along with hemoglobin and other plasma proteins.

Question 14

Thrombotic Microangiopathies

Answer 14

refers to lesions seen in various clinical syndromes characterized by microvascular thrombosis accompanied by microangiopathic hemolytic anemia, thrombocytopenia, and, in certain instances, renal failure.

Question 15

Common primary forms of Thrombotic Microangiopathies

Answer 15

Shiga toxin–mediated hemolytic uremic syndrome (HUS); atypical HUS, also called complement-mediated TMA because excessive complement activation is an important pathogenic mechanism; thrombotic thrombocytopenic purpura (TTP) ; and some of the drug-mediated TMAs. Malignant hypertension and scleroderma-associated TMA represent examples of the secondary forms.

Question 16

The major pathogenetic factors in the thrombotic microangiopathies

Answer 16

endothelial cell injury and platelet activation and aggregation. They can be caused by diverse insults, including external toxins, drugs, autoantibodies, and inherited mutations, which can lead to excessive small vessel thrombosis in the capillaries and arterioles in various organs.

Question 17

result in the formation of abnormally large vWF multimers that activate platelets spontaneously, leading to platelet aggregation and thrombosis in multiple organs, including the kidney.

Answer 17

Deficiencies of ADAMTS13

Question 18

ADAMTS13

Answer 18

(a disintegrin and metalloprotease with thrombospondin-like motifs), a plasma protease that cleaves von Willebrand factor (vWF) multimers into smaller sizes.

Question 19

thrombotic thrombocytopenic purpura (TTP)

Answer 19

caused by acquired or inherited deficiencies in ADAMTS13

Question 20

caused by acquired or inherited deficiencies in ADAMTS13

Answer 20

thrombotic thrombocytopenic purpura (TTP)

Question 21

The morphologic lesions in all forms of TMA regardless of the etiology

Answer 21

Thrombi are seen in glomerular capillaries and also the arterioles and sometimes the larger arteries in more severe cases. Additional glomerular changes resulting from endothelial injury include widening of the subendothelial space, duplication or splitting of GBMs, and lysis of mesangial cells. Cortical necrosis also may occur in severe cases. If TMA persists, scarring of glomeruli may develop. Except for varying amounts of fibrinogen in the glomeruli and arterioles, immunofluorescence studies are typically negative.

Question 22

one of the main causes of acute kidney injury in children

Answer 22

Shiga toxin–mediated HUS due to
Shiga toxin–producing E. coli Shigella dysenteriae serotype 1

Question 23

An emerging theme in the pathophysiology of the hereditary cystic diseases of the kidney

Answer 23

the underlying defect is in the cilia-centrosome complex of tubular epithelial cells

Question 24

the most common form of cystic renal disease in childhood

Answer 24

Renal dysplasia

Question 25

Acquired cystic kidney disease

Answer 25

occurs in patients with end-stage renal disease who have undergone dialysis for many years. Multiple cysts may be present in both the cortex and the medulla and may bleed, causing hematuria. The risk for renal neoplasms, particularly cystic ones, in this setting is over 100 times greater than in the general population.

Question 26

Autosomal Dominant (Adult) Polycystic Kidney Disease
Most common defect

Answer 26

In 85% to 90% of families, PKD1, on the short arm of chromosome 16, is the defective gene. This gene encodes a large (460-kDa) and complex cell membrane–associated protein called polycystin-1.

Question 27

Polycystin-1

Answer 27

Polycystin-1 localizes to the primary cilium of tubular cells (as do nephrocystins linked to medullary cystic disease, discussed later), giving rise to the concept of renal cystic diseases as a type of ciliopathy.

Question 28

Autosomal Dominant (Adult) Polycystic Kidney Disease
Second most common defect

Answer 28

The PKD2 gene, implicated in 10% to 15% of cases, resides on chromosome 4 and encodes polycystin-2, a smaller, 110-kDa protein. Polycystin-2 is thought to function as a calcium-permeable membrane channel, and is also localized to cilia. Although structurally distinct, polycystins 1 and 2 are believed to act together by forming heterodimers. Thus, mutation in either gene gives rise to essentially the same phenotype, although patients with PKD2 mutations have a slower rate of disease progression compared to patients with PKD1 mutations.

Question 29

Autosomal Recessive (Childhood) Polycystic Kidney Disease

Answer 29

All types result from mutations in the PKHD1 gene, coding for a putative membrane receptor protein called fibrocystin. Fibrocystin is found in cilia in tubular epithelial cells, but its function remains unknown.

Question 30

an underappreciated cause of chronic kidney disease that usually begins in childhood

Answer 30

Nephronophthisis–medullary cystic disease complex

Question 31

Nephronophthisis–medullary cystic disease complex

Answer 31

a cause of chronic kidney disease in children and young adults. Of autosomal recessive inheritance, it is associated with mutations in several genes that encode epithelial cell proteins called nephrocystins that may be involved in ciliary function; the kidneys are contracted and contain multiple small cysts.

Question 32

The cause of stone formation

Answer 32

The most important cause is increased urinary concentration of the stone’s constituents, so that it exceeds their solubility in urine (supersaturation).

Question 33

Calcium oxalate deposition can be seen is what conditions?

Answer 33

nonspecific finding in patients with acute tubular injury. However, the differential diagnosis also includes oxalate nephropathy. Known causes of oxalate nephropathy include primary hyperoxaluria, ethylene glycol intoxication, enteric hyperoxaluria (e.g., due to gastric bypass, chronic pancreatitis, small bowel resection, or malabsorption), vitamin B6 deficiency, excessive indigestion of vitamin C or dietary substances rich in oxalic acid (parsley, nuts, star fruit, sweet tea, etc.), and various drugs (e.g., methoxyflurane, Orlistat, Praxilene, COX-2 inhibitors), among others.