8 ) Secondary nephropathies: gout, myeloma and diabetic nephropathy

Question 1

what are the types pf gout nephropathy ?

Answer 1

there is acute and chronic

Question 2

pathophysiology of acute gout nephropathy ?

Answer 2

deposition of uric acid crystals within the kidney medullary interstitum predominantly in collecting ducts. ALSO renal pelvis, or ureter.

This obstruction is usually bilateral, and patients follow the clinical course of acute kidney failure.
= oliguric and anuric

= most often in tumor lysis syndrome than gout

Question 3

what is the etiology of hyperurecmia ?

Answer 3

idiopathic - aggregated by poor diet

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secondary - decrease - uric acid secretion
by medications such as aspirin and loop diuretics

chronic renal insufficiency

enzyme deficisny in metabolism of purine
Lesch-Nyhan syndrome = X-linked deficit of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)

phosphoribosyl pyrophosphate deficiency

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diet rich in purine = red , meat and sea food

Question 4

what is the pathophysiology in chronic gouty nephropathy ?

Answer 4

chronic tubulointerstitial nephritis, induced by deposition of monosodium urate crystals in the distal collecting ducts and the medullary interstitium (loop of henle as well as collecting ducts here)

Question 5

what is a clinical feature of gouty nephropathy ?

Answer 5

uric acid nephorlithiasis
hypertension
decrease production of urine
pain in joints

Question 6

what is the diagnosis of chronic gout nephropathy ?

Answer 6

two of the following criteria :

atleast two attacks of painful joints

clear observation gout in podagra

presence of tophus

rapid response to colchicine within 48hrs of treatment initiation

definitive : presence of monosodium rate crystals seen in synovial fluid or tissues

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serum uric acid

uric acid/ creatinine ratio is more than 1

hyperurecemia

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us - renal calculi

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kidney biopsy -

Polarized light microscopy: needle-shaped monosodium urate crystals that are negatively birefringent

tophus formation/ granuloma : large aggregations of urate crystals surrounded by an intense inflammatory reaction of macrophages,lymphocytes and large foreign body giant cels engulfing the crystals cortico-medullary junction and deep in the medulla

tubules distended by a collection of needle-like spaces which contained urate crystals

later becomes associated with the findings of
associated with hypertensive kidney disease: advanced arteriosclerosis, glomerulosclerosis,
and interstitial fibrosis.

Question 7

what is the treatmnet of gouty nephropathy ?

Answer 7

lifestyle modification and dietary changes such as 
no alcohol, 
reduced meat 
purine free diet 
achieve ideal BMI 

nsaids - diclofenac , indomethacin
or cox -2 inhibitors - celecoxib

allopurinol - do not use it if there is an acute gout attack

febuxostat

rasburicase

can add colchicine to reduce the frequency of attacks

increase the urine output - 3l of water a day

increase the urine ph
by giving potassium citrate or sodium bicarbonate

if all above fails hemodialysis

Question 8

who does multiple myeloma usually affects ?

Answer 8

older population
and mainly they are men

renal failure is the second most frequent cause of death in multiple myeloma

Question 9

WHAT ARE THE OTHER CLINICAL FEATURES OF mm ?

Answer 9

predominantly those of the myeloma 
on bones - bone pain - back pain 
hypercalcemia 
fractures 
anemia 
pneumococcal infection

cast nephropathy usually presents with acute kidney injury - oliguria due to urinary tract obstruction

Question 10

the type of kidney disease presented by multiple myeloma can be classified into ?

Answer 10

glomerular
primary amyloidosis - mesangial deposits

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tubular
light chain cast nephropathy
affecting
distal tubular dysfunction

proximal tube dysfunction - acquired falconi syndrome = wasting of amino acids, glucose, phosphate, uric acid, and various ions

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interstitial
plasma cell infiltration
interstitial nephritis

Question 11

what is the pathophysiology of cast nephropathy ?

Answer 11

in multiple myelom aproximal tubular cells are overwhelmed and light chains
saturate the reabsorptive capacity

reach distal nephron, where they are directly toxic to epithelial cells; Bence Jones proteins combine with urinary glycoprotein (Tamm-Horsfall) under acidic conditions to form tubular casts that obstruct tubules

myeloma kidney or myeloma cast nephropathy generally refers to renal insufficiency caused by the tubulointerstitial damage that result

Question 12

what is the diagnosis of MM ?

Answer 12

lab
anemia normochromicand normocytic
Hypercalcemia, hyperuricemia
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urine
proteinurea often light chain protein known as
bence jones protein
casts composed of
protein electrophoresis in urine or immunofixation

monoclonal light chain protein and TAMM horsfall protein secreted by the thick ascending limb of henle

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x ray
bone fractures

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kidney biopsy
light chains casts located within the distal tubules - ranging from needle shaped crystals to irregular polygonal shapes with sharp edges
several casts engulfed by giant cells
stain very minimal with PAS

mixed red and blue staining with masson trichrome stain

pct show acute tubular injuries - with the loss of apical briush border

IF staining of k light chain in casts
or granular dense material along the basement membrane

Question 13

what increases the risk of myeloma nephropathy therefor can be used to manage the patients ?

Answer 13

Low urine flow = prevention of volume depletion (eg, using normal saline for volume expansion) to maintain a high urine flow rate

Radiocontrast agents

Hyperuricemia

NSAIDs

Elevation of luminal sodium chloride concentration (eg, due to a loop diuretic)

Increased intratubular calcium due to the hypercalcemia that often occurs secondary to bone lysis in multiple myeloma

Question 14

how can we treate myeloma nephropathy ?

Answer 14

Plasma exchange may be tried to remove light chains.

Alkalinization of the urine to help change the net charge of the light chain and reduce charge interaction with Tamm-Horsfall mucoprotein may make the light chains more soluble.

Colchicine may be given to decrease secretion of Tamm-Horsfall mucoprotein into the lumen and to decrease the interaction with light chains, thus decreasing toxicity.

Loop diuretics may be avoided to prevent volume depletion and high distal sodium concentrations that can worsen myeloma-related kidney disease.

Question 15

what is the characterisation of diabetic nephropathy ?

Answer 15

chronic condition developing over many years

by gradual increase in urinary albumin excretion - nephrotic syndrome

high blood pressure

decreasing GFR

absence of other renal tract disease

presence of diabetic retinopathy / neuropathy

Question 16

what is the pathophysiology of diabetic nephrotphathy ?

Answer 16

hypertension which is a common comorbidity with

glycated enzymes - glucose attach to nitrogen molecules such as lysine = easing to schiff base
the shiff base goes into ketone - crosslinks between lysin and arginine - and if the cross linking occur collagen or basement membrane - damages - and get more damaged

increase protein kinase c - because increased
diacyl glycerol - because increase of glycolysis pathway - because increase of glucose
= increase vascular perm

also non enzymatic glycosylation of basement membrane - increasing the perm

also

vasoconstriction of the efferent arteriole - because of RASS - hyperglycemia causes a an activation of the RASS (maybe because of polyuria there is low fluid volume )

interglomerular hypertension - increase the GFR

the mesangium has extracellular matrix the collagen network which holds the capillary in place = they can cause the capillaries in the glomeruli to
constrict or dilate
and they have the ability to release cytokines in reaction to injury

the mesangium is going to react by releasing cytokines - leading to inflammation
and there is mesangial explanation - due to hypertrophy of the mesangium and proliferation
thickening of the basement membrane

there is increase in the mesangial matrix - firbin and collagen increase - leading to glomerulus atrophy and dysfunction

= leading to hyaline glomerulosclerosis =
which further narrows the vessels - hypertension , decrease in GFR
it affects both efferent and afferent arterioles

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1) increase in GFR
2) proteinurea - mesangial expansion and increase in the matrix or the fenestra
3) microhematurea
because of injury to the tubules due to ischemia - collagen fibrils accumulate in the glomerulus - decrease the blood flow to the efferent arteriole and it supplies the tubules

4) decrease in GFR
5) ERD

Question 17

what is the difference between hypertensive neproathy and diabetic nephropathy

Answer 17

hypertensive nephropathy is disease of the afferent arteriole

while diabetic nephropathy is more the disease of the mesngium

even though both start with high GFR
but it will not pass through a phase of protein urea because this is due to the contraction of the mesangial cells

however 3-5 is shared in common

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hyaline glomeruscleorisis occurs in the afferent and efferent arterioles whilst in diabetic nephropathy while in hypertensive nephropathy it majorly affects the afferent arterioles

Question 18

what are the clinical features of diabetic nephropathy ?

Answer 18

in type 1 its more severe
onset within 5-10 years

tye 2 - more than 10 years

first symptom is quite frequent urination - increase GFR - polyurea , polydipsia , polyphasgia ,

generally they are asymptomatic until they get to end stage renal disease

ureic polyneuropathy in later stages

Question 19

diagnosis of diabetic nephropathy ?

Answer 19

first sign you see for diabetic nephropathy : albuminuea
moderate albuminurea = 30-300mg = cannot burin dipstick detected
its important because this is the time we can prevent

it can lead to severe albuminuria / nephrotic syndrome = more than 300mg = which is urine dipstick decade
which will lead to ESRD

GFR - high
then going low

creatinine is also a measure of GFR
it first is low then becomes high

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kidney biopsy

earliest change - diffuse and thickened basement membrane

then mesangial hypercellularity

mesangium nodules or sclerosis - = known as kimmel stein wilson nodule

with time hyaline sclerosis of of glomeruli

Question 20

risk factors increase DN ?

Answer 20

family history
duration
glycemic control
hypertension
smoking
race - african american , mexican american
diabetic retiinopathy - because it usually occurs BEFRE diabetic nephropathy

DM1

Question 21

what is the treatmnet of DN ?

Answer 21

good glycemic control

aceI - renal protectors , lowers hypertension
and decrease protein (decrease the interglomerular hypertension)

protein restriction

blood pressure control - early antihypertensive treatment delays the progression of diabetic neuropathy

reduce daily salt intake

and weight loss

hemodilaysisi

renal transplant