Biochem

Question 1

Key enzymes located in renal medulla

Answer 1

Hexokinase
Phosphofructokinase
Pyruvate kinase

Question 2

Key gluconeogenic enzymes found in renal cortex

Answer 2

Pyruvate carboxylase
Phosphoenolpyruvate (PEP) carboxykinase
Fructose-1,6, -biphosphate
Glucose-6-phosphate

Question 3

Energy requirment for renal medulla and end product? ONLY part of kidney that has all enzymes for gluconeogenesis

Answer 3

Glucose
Lactate (not CO2 and water)
Proximal tubule

Question 4

Insulin and glucagon in kidney

Answer 4

Insulin: suppress glucose release
Glucagon: no effect on kidney
Kidney in contrast to liver because glucose release is increased after glucose ingestion

Question 5

Metabolic fate of glucose in medulla? Cortex?

Answer 5

Medulla: obligate user of glucose (anaerobic) for energy (lactate end product)
Cortex: uses very little glucose, relies mainly on beta-oxidation of FFAs
Major energy requiring process in kidney is glucose reabsorption from glomerular filtrate in PCT

Question 6

Filtered glucose is reabsorbed via

Answer 6

Two sodium dependent glucose co-transporters (SGLTs)
SGLT2: reabsorbes 90% glucose, low affinity-high capacity, in S1 segment. Associated with GLUT2
SGLT1: 10% glucose, high affinity-low capacity, located in S3, associated with GLUT1. TYPE 2 DIABETES MELITUS RE-ABSORPTIVE CAPACITY OF SGLT1 INCREASES BY 20%

Question 7

Familial renal glucosuria (FRG)

Answer 7

Detectable amounts of urinary glucose at normal blood glucose concentrations
due to SLC52A (codes for SGLT2) mutation
mild glucosuria: heterozygous mutation
severe: homozygous or compound heterozygous

Question 8

Glucose-galactose malabsorption syndrome (GGM)

Answer 8

Severe osmotic diarrhea, dehydration, and shock soon after glucose or galactose introduced into diet after birth
Mild glucosuria

due to SLC51A1 (encodes SGLT1) mutation
Autosomal recessive

Question 9

Fanconi syndrome (aka De Toni-Fanconi syndrome)

Answer 9

Glucosuria in the setting of global impairment of proximal tubular function (also causes hypophosphatemia, hypouricemia, renal tubular acidosis and aminoaciduria)
presents with polyuria, polydipsia, dehydration, fever, bone deformities and fucked up growth
2 degree to inherited defects (see slides)
Cytinosis

Question 10

Fanconi-Bickel syndrome (FBS)

Answer 10

presents at 3-10 months with combination of hepatomegaly (due to glycogen accumulation), Fanconi-type nephraopathy with severe renal glucosuria, hypoglycemia in the fasted state, and glucose/galactose intolerance in the fed state, and glucose/galactose intolerance in the fed state

due to mutations in the GLUT2 gene (autosomal-recessive). Expressed in both hepatocytes and at basolateral membrane of proximal tubules

Question 11

Once in the kidneys glutamine is taken up and metabolized to

Answer 11

Ammonium ion (NH4+): acid-base balance, increased glutamine uptake in acidosis (metabolic and respiratory), results in compensatory increase of NH4+ excretion in urine

Alpha-ketogluterate, used for: glucose production, oxidized CO2 (TCA cycle), converted to alanine (via tranaminase)

Question 12

Renal mucin

Answer 12

Mucin 1: encoded by MUC1 gene, heavily glycosylated protein located on apical surface of tubular cells, provides protective covering to lumina in the kidney, has signal transduction functions

Question 13

Autosomal dominant tubulointerstitial kidney disease (ADTKD)

Answer 13

Bland urinary sediment with minimal blood and protein
Pathological changes: tubular and interstitial fibrosis, slowly progressive CKD
Caused by MUC1 frameshift mutation (also caused by mutations in the uromodulin gene), mutant protein aggregates and deposits in tubular cells (conformational disease)

Question 14

Blood urea nitrogen (BUN)

Answer 14

Cleared by kidneys
PROS: well-established, measured cheaply & easily
Routinely measured in serum (enzyme/oxidation reaction assay)
CONS: levels affected by non-renal influences (protein intake, dehydration, liver function, GI bleeding, steroid use)

Assay often underestimates renal function due to interfering chromogens

Question 15

Creatinine

Answer 15

Cleared by kidneys
PROS: well-established; measured cheaply and easily.
Measured in serum & urine: jaffe rate, high performance liquid chromatography (most sensitive, unaffected by chromogens)
Serum level used to estimate GFR
CONS: levels affected by non-renal influence, lacks sensitivity when renal impairment mild

Question 16

Cystatin C

Answer 16

Cysteine protease inhibitor produced by uncleared cells/released into blood
Reabsorbed & catabolized by kidney tubules
PROS: recently emerged and reliable, serum level measured by immunonephelometry or ELISA
CONS: affected by steroid use or thyroid dysfunction

Question 17

Uric acid

Answer 17

End product of purine catabolism; excreted by kidneys

circulating levels increase during renal impairment in CKD: predicts greater risk of end-stage renal disease

Question 18

Kidney injury molecule-1 (KIM-1)

Answer 18

Transmembrane protein expressed on the luminal surface of injured proximal tubules
increased urine levels with tubulointerstitial damage correlate with increased renal expression

Question 19

Neutrophil gelatinase associated lipocalin (NGAL)

Answer 19

Iron-transporting protein almost entirely reabsorbed by tubules in the normal kidney
Very good marker of acute kidney injury (indicates defects in proximal tubular reabsorption and in the distal nephron)

Question 20

Bio markers of renal oxidative stress

Answer 20

OS evident in patients with moderate to severe CKD
Advanced glucagon end products (AGEs): irreversibly cross-linked derivatives of sugar/macromolecule complexes, increased formation during OS, accumulate in blood of diabetic and uremic patients

Pentosidine: serum and urine levels detected by HPLC or ELISA, predicts development of diabetic nephropathy

Question 21

Biomarkers of renal fibrosis

Answer 21

TGF-beta1 & connective tissue growth factor: promote renal fibrosis, increase urine levels with progressing CKD
TGF-beta-inducible gene H3 (Big-H3), levels 1000X greater than TGF-beta1 in diabetes
Plasminogen activator inhibitor-1: levels correlate with renal injury and fibrosis in diabetic nephropathy and progressive chronic glomeruclonephritis

Collagen type IV: major component of kidney ECM (increases with progression of renal fibrosis), increased urine levels elevated in IgA nephropathy and diabetic nephropathy

Question 22

IgG renal biomarker

Answer 22

Fractional excretion predicts progression of primary focal segmental glomerulosclerosis (FSGS) and its response to treatment

Question 23

IgA

Answer 23

Urine levels can indicate renal damage severity in IgA nephropathy and correlate with proteinuria, serum creatinine and glomerulosclerosis in this disease

Question 24

IgM

Answer 24

Urine levels strong predictor of disease progression for anti-nuclear cytoplasmic antibody-associated vasculitis

Question 25

Interleukin-18

Answer 25

Pro-inflammatory agent produced by leukocytes, vessel, kidney tubules
Increased production by tubules during acute renal injury
Increased urine levels sensitive and specific marker of acute tubular necrosis (ATN) and delayed graft function in post-ischemic kidney

Question 26

Monocyte chemoattractant protein-1 (MCP-1) or aka CC-chemokine ligand 2

Answer 26

Attracts monocytes and macrophages

Urine levels correlate with interstitial macrophage accumulation in lupus nephritis and diabetic nephropathy

Question 27

Interferon-inducible protein 10 (IP-10) aka CxCL10

Answer 27

Attracts activated T cells

Urine levels increase in diabetic nephropathy and renal allograft rejection

Question 28

CXC-chemokine ligand 16 (CXCL16)

Answer 28

Attracts activated T cells
Urine levels correlate with T-cell accumulation in acute and chronic renal diseases
Urine levels increase in lupus nephritis or renal allograft rejection