Week 4 Flashcards
cause of diabetic nephropathy?
structural and functional changes to GBM hyperglycemia inc GBM collagen type IV, inc fibronectin, inc reactive oxidative species, Increased circulating AGEs (normally excreted in urine)
glycosylation of proteins damage GBM (thickening)
2) Hemodynamic changes leads to glomerular hypertrophy (sclerosis)
classes of diabetic nephropathy?
Class I: isolated glomerular basement membrane thickening
Class II: mild to severe mesangial expansion (from glycation of membrane proteins)
Class III: at least one Kimmelstiel-Wilson lesion (intercapillary glomerulosclerosis)
Class IV: >50% global glomerular sclerosis
RFs for diabetic nephropathy?
family history, advanced age, concurrent HTN, poor glycemic control (>6.5%
HbA1c levels), ethnicity (increased incidence and severity in Blacks, Mexican-Americans, Pima Indians—often due to socioeconomic factors) obesity, smoking, oral contraceptives
ssxs of diabetic nephropathy?
albuminuria, occ hematuria, along with concurrent diabetic symptoms
what do you need to monitor in a diabetic nephropathy pt?
microalbumin (normal 0-30): Immunologic measurement of microalbumin in urine is now considered a standard of care for management of diabetes mellitus and the early detection of diabetic complications. HbA1c levels (normal 4%-5.9%, prediabetes 6-6.4%, diabetes greater than or equal to 6.5%)
w/o intervention what % of DMT1 with repeated elevations will progress to ESRD?
% with DMT2 will progress to nephropathy?
DMT1: 80% will progress to ESR
DMT2: 20-40% with sustained levels will progress to nephropathy
concomitant diabetes related diseases aside from nephropathy?
neuropathy and retinopathy
goals for HbA1c, FPG, BP, postprandial BG, LDL, HDL, TGs for diabetic pts?
HbA1c less than or equal to 6.5% FPG less than 110 mg/dL postprandial PG less than 140 BP less than 130/80 LDL less than 100 HDL greater than 40 in men, greater than 50 in women TGs less than 150
general guidelines for pre-diabetic pt?
FPG 100-125 whole foods diet sufficient sleep exercise 150 min/wk limit EtOH consumption avoid tobacco stress reduction natural remedy support (?)
additional herbs and foods to tx diabetes?
ginkgo flax and pumpking seed curcumin guggul chromium ALA, vaccinium
renovascular dz is a major cause of what? associated with what other dz processes?
major cause of ESRD, esp in elderly
high-renin HTN associated w/increased rate of cerebro and CV complications
causes of renovascular HTN?
atherosclerosis fibromuscular dysplasias polyarteritis nodosa post-transplant stenosis aortic dissection
prevention of renovascular HTN?
lifestyle changes to reduce the risk of HTN exercise lose weight if overweight dietary adjustments to help control HTN modify sodium intake
pathogenesis of renovascular HTN?
Reduced blood flow causes affected kidney(s) to secrete renin, retain NaCl and H2O which inc BP
Hypersecretion of renin also caused by sodium depletion, hemorrhage, shock, CHF, renal A stenosis
PMHx of renovascular HTN?
GN, chronic PN, hydronephrosis, urolithiasis, renal trauma, radiation therapy to the abdomen, Wilm’s tumor
SSXS of renovascular HTN?
May be no symptoms
HA, fatigue, confusion, vision changes, angina-like chest pain, heart failure, hematuria, epistaxis, irregular heartbeat, ear noise or buzzing, pulmonary edema
Difficult to control HTN
Sudden aggravation of earlier well-controlled HTN in elderly
PE: Abdominal bruit over renal A
Signs of complications: left ventricular hypertrophy, hypertensive retinopathy
BP that gives you moderate and high clinical index of suspicion for renovascular HTN? labs you want to measure for renovascular HTN? challenge test for captopril challenge test? imaging for renovasular HTN?
moderate: BP >120 mmHg, HTN refractory to therapy
measure CBC, electrolytes, glucose, BUN, creatinine, UA, ECG, plasma renin
captopril challenge test
high: severe HTN w/progressive renal insufficiency, refractory to aggressive therapy, malignant HTN, elevated Cr
imaging: renal arteriography, doppler U/S of renal arteries, magnetic resonance angiography, CT
tx and management considerations of renovascular HTN?
1) Control BP with meds: diuretics, beta-blockers, Ca channel blockers, ACE inhibitors, angiotensin receptor blockers (ARBs) and alpha blockers—–response variable Monitor doses as needed!
2) Percutaneous transluminal angioplasty (insertion of a stent)
3) Surgical reconstruction of damaged artery
4) Surgical bypass of renal arteries in cases of fibromuscular hyperplasia
5) Treat atherosclerosis: guggal, garlic, EFAs, B vits
6) Vascular protectants: bioflavonoids, vaccinium
complications of renovascular HTN?
early death, heart dz/MI/CHF, stroke, loss of vision
cause of benign HTN neprosclerosis? can progress to?
Chronic HTN damages microvasculature, glomeruli, tubules, interstitial tissues leading to nephrosclerosis. Over years may progress to end stage renal disease (common!)
RFs for benign HTN nephrosclerosis?
Risk factors: aging, poorly controlled HTN, DM, more common in blacks
findings on UA for benign HTN nephrosclerosis? imaging results?
UA: mild proteinuria, increasing BUN and creatinine levels, hyperuricemia
imaging: small KDs
ssxs of renal artery occulsion? UA findings? what can develop? imaging?
ssxs: flank pn, abd pn, fever, N/V
UA: hematuria
acute renal failure may develop
imaging: CT angiography
renal vein thrombosis leads to what? causes? ssxs? imaging?
leads to occlusion of 1 or both renal veins
causes: hypercoagulability, nephrotic syndrome, amyloidosis, E therapy, PG, SLE
ssxs: renal failure, occ N/V, flank pn, gross hematuria, decreased urine output
imaging: magnetic resonance venography, doppler U/S
what is nephroptosis? theorized causes?
floating or falling KD
KD drops greater than 5 cm upon supine to standing
theorized to be dt lack of perirenal fat and fasical support and pt may also have longer than normal renal vascular pedicle
nephroptosis is MC in what gender, body habitus?
F 5-10:1, young and thin
more common on R side
64% of those with fibromuscular dysplasia of the renal artery have what other condition?
nephroptosis
RFs for nephroptosis?
excessive wt loss, frequent intense physical activity
ssxs of nephroptosis?
severe abd, CV, flank pn, vomiting in upright position from acute hydronephrosis kinked primal ureter, renal vessel lumen narrowing and resultant ischemia as well as visceral nerve stimulation from traction
what is a dietl crisis? how is pn relieved?
severe colicky flank pain, nausea, vomiting, chills, tachycardia, oliguria, hematuria and proteinuria
pn relieved with upward movement of the KD, supine position
PE of nephroptosis?
KD palpable in ipsilateral lower abd
w/u of nephroptosis?
renal U/S, IV urography (erect and supine films), look for hydronephrosis
tx of nephroptosis?
surgical nephropexy for sx pts w/flank pn >1yr
laprascopic nephropexy fro sx pts
wear a truss, support connective tissue
post-surgical support: HP arnica, ledum; ligaplex, vit C, vit A, zinc
ddx of nephroptosis?
urolithiasis, cholecystitis, spastic bowel, PN, ovarian cyst, appendicitis, diverticulitis
forms of acquired cysts?
simple or solitary cysts
acquired cystic KD dz
65-70% of all renal masses usu found incidentally, often located in outer cortex and contain fluid consistent with an ultrafiltrate of plasma. Usu asymptomatic, but may become infected, or if large may block ureter and cause hydronephrosis.
Average size: 10cm
simple or solitary cyst
ddx of simple or solitary cyst?
malignancy, renal abscess, polycystic KD dz
ssxs of simple or solitary cyst?
flank or back pn, intermittent and dull, fever and malaise if infected, abd mass may be palpated or percussed, tender if infected
UA results simple or solitary cyst?
U/S will show what?
CT will show what?
normal UA, rare microscopic hematuria
U/S - criteria for simple benign cyst, echo - free, sharply demarcated with smooth walls, enhanced back wall indicating good transmission through the cyst
CT: smooth thin wall, sharply demarcated, should not enhance with contrast
tx of simple or solitary cysts?
if simple, leave alone
constitutional HP
if infected abx, may need perQ drainage (U/S guided)
surgical excision may be required if obstructing ureter
multiple cysts found in patients without a hereditary link. Seen with patients on dialysis and CKD. “Dialysis Cysts” Theorized mechanisms of cyst development: tubule block and fluid accumulation; tubule hyperplasia from growth factors and activation of oncogenes; kidney atrophy from long standing ischemia leading to parenchymal acidosis.
acquired cystic kidney disease
7 forms of hereditary cystic KD dzs?
autosomal dominant polycystic KD dz autosomal recessive PKD medullary sponge KD medullary cystic KD dz juvenile nephronophthisis glomerulocystic KD dz multicystic dysplastic KD
Most common hereditary dz in US, almost always bilaterally enlarged kidneys with multiple cysts of various sizes.
Incidence: 1:400-1000 persons, 6000 new cases/yr,
SSX appear ~30-40yo: Most patients have normal kidney function until 4th decade
50% may also have hepatic, pancreatic, splenic or CNS arachnoid cysts
autosomal dominant polycystic KD dz
dx requirements for autosomal dominant polycystic KD dz?
15-39 : 3 cysts in both KDs; 40-59 : at least 2 cysts and positive FHx
ddx of autosomal dominant polycystic KD dz?
B/L hydronephrosis B/L RCC (rare) tuberous sclerosis simple cysts Von-Hippel Lindau syndrome
ssxs of autosomal dominant polycystic KD dz?
Pain over both kidneys due to infection, obstruction, hemorrhage, “drag” from heaviness
Gross or microscopic hematuria; nocturia
HTN (retinopathy can develop)
Palpable, nodular kidney(s)
Developing renal insufficiency: HA, N&V, weight loss
If infected: fever, chills, tender kidney(s)
autosomal dominant polycystic KD dz will show what on labs? UA? imaging?
labs: increased EPO leading to increased Hgb and Hct, anemia from blood loss
UA: proteinuria, hematuria, possibly pyuria and bacteriuria if infxn
progressive uremia from renal insufficiency (increased BUN and Cr), dec GFR
imaging: KUB shows enlarged renal shadows up to 5x size
CT 95% accurate for dx, can detect cysts from 0.5 cm
U/S can detect cysts from 1-1.5 cm, most cost effective START HERE
MRI can differentiate RCC from cysts
complications of autosomal dominant polycystic KD dz?
gross hematuria nephrolithiasis HTN ESR increasing, intractable pn can also see cerebral aneurysm, MVP, aortic aneurysm, colonic diverticula
general tx measures for autosomal dominant polycystic KD dz?
low protein
force fluids to 3000 mL or more per day to suppress vasopressin and control BP
restrict caffeine
flax oil
reasonable physical activity - avoid strenuous activity or contact sports
treat uremia, stones, infxn
screen for and treat HTN, recommend ACEIs, antgiotension II receptor antagonist blockers
possibly dialysis, renal transplantation, cystic decompression (for pn)
constitutional HP - baryta carb, calc carb, phosphorous
constitutional hydro
conventional drug trials: somatostatin, everolimus
prognosis of autosomal dominant polycystic KD dz? cause of death typically?
for children very poor
ssxs presenting after 35-40 yo are more favorable but may only live about 5-10 yrs post dx
cause of death typically cardiac or neurologic
Mutation of PKHD1 gene (prenatal testing available)
Rare, boys>girls
Severity varies: may lead to death in newborn, if survive, may lead to ESRD and the need for Ki transplant by age 10 or 15. Some not diagnosed until age 2
Microcysts develop in medulla and cortex (look like pin-point dots) and dilatation of the collecting ducts. Over time, larger cysts develop with interstitial fibrosis and loss of renal function
The disease is also associated with biliary dysgenesis. Leads to hepatomegaly and portal hypertension in most cases
autosomal recessive polycystic KD dz
ssxs of ARPKD?
abd pn, abd mass, polyuria, polydipsia, HTN, hepatomegaly, spleomegaly
UA of ARPKD? labs? imaging results? treatment?
UA: reduced urine osmolality, pyuria
labs: hyponatremia, bilirubin and liver enzymes mb elevated, thrombocytopenia
see on U/S: B/L lg echogenic KDs
tx is supportive care
congenital but not diagnosed until 20s or 30s, rare, unknown cause, more common in F
“Renal tubule duct ectasia” Cysts/sacs in tubules or collecting ducts, block urine flow. Often asx, but can cause urinary tract infections or stones (and associated sx) can lead to renal failure in 10% cases.
Seen on US or CT
medullary sponge kd
Uncommon, slowly progressing kidney disease manifesting usually in teens with variable rates of progression to ESKD. Cysts are not always seen on U/S.
Bland urine sediment with minimal proteinuria
Three possible genetic causes: UMOD gene mutation (leads to gout), REN gene mutation (low BP, anemia, hyperkalemia, hyperuricemia) and MUC1 gene mutation (no distinguishing characteristics)
medullary cystic KD dz
Hereditary. Fluid filled cysts in corticomedullary region (loss of coricomedullary differentiation), causes fibrosis and thickening of tubular basement membrane. Normal to small kidneys. Hepatic fibrosis also often seen.
Symptoms develop after one year of age, insidious onset of renal failure to ESKD
Juvenile nephronophthisis
ssxs of juvenile nephronophthisis?
polyuria, polydipsia, fatigue, nausea, anorexia, bone growth abnormalities, often Normal BP, NPH has also has eye (retinal degeneration) problems
UA and labs of juvenile nephronophthisis? dx? tx?
UA: low urine osmolality, proteinuria
labs: hypernatriuria, hyponatremia, elevated Cr, anemia, metabolic acidosis, hypovolemia
dx: (+) genetic test (NPHP1 deletion), U/S, renal bx
tx by correcting volume and electrolyte imbalances, renal transplantation preferred therapy
Rare, usu diagnosed in neonatal period, more often unilateral. Enlarged kidneys with cysts on glomeruli. Can be associated with DMI and genetic conditions like Trisomy 13
glomerulocystic KD dz
Congenital mal-development where renal cortex is replaced by various sized cysts without remaining functional tissue. Bilateral manifestation would be incompatible with life. The cysts anchored in the renal parenchema resemble a bunch of grapes. The renal calyce is absent.
Seen on U/S, then follow up radionucleotide imaging
SSX palpable abdominal mass, abdominal pain, incontinence, recurrent UTI
multicystic dysplastic KD
autosomal dominant neurocutaneous dysplasia complex leading to increased vascular endothel. growth factor; resulting in retinal angiomas, hemangioblastomas, pheochromocytoma, islet cell tumors, renal cysts, epididymal cysts
SSX begin in 2nd to 3rd decade. Eye: retinal hemorrhage, detachment, glaucoma. Headaches, ataxia
Von-Hippel Lindau syndrome
autosomal dominant
Causes CNS lesions and white matter abnormalities as well as lesions in skin, heart, lungs, kidney, skeleton, liver.
SSX seizures, mental retardation, adenoma sebacum (facial angiofibroma)
tuberous sclerosis
MC type of benign renal tumor? comes from where? located where? ssxs?
renal adenoma from glandular tissue
small, well-differentiated glandular tumors of renal cortex
asx, usu identified on autopsy or “incidentaloma” found during workup of another condition
5 other rare, benign renal tumors? (think different types of tissues)
leiomyomas hemangiomas lipomas, angiomyolipoma juxtaglomerular cell tumor renal pseudotumor
where does an adenocarcinoma/RCC come from 85% of the time? other 15%? what %age of pts will have mets if have RCC?
85% of the time from renal glandular tissue
15% of the time from transitional cell carcinoma in the renal pelvis
25-30% of pts will have METs at dz presentation (eek)
highest prevalence in ethnicity? lowest?
highest in black and Hispanic males
lowest in Asian Americans and Pacific Islanders
RFs of RCC?
smoking HTN chronic analgesic use (NSAID and non-NSAIDs) obesity toxin exposure (Cd, asbestos, Pb, gas, petroleum products, PAHs) cytotoxic chemo sickle cell dz nephrolithiasis nitrites in diet prior radiation therapy OCPs high coffee intake animal fat diet dialysis hysterectomy contrast IV
where does RCC specifically originate? what does it do to the shape of the KD?
originates from proximal renal tubular epithelium in the cortex
leads to characteristic nodule, distorted, bulging shape of the KD
how can RCC spread?
direct invasion through renal capsule into adjacent structure or direct extension into renal vein
where does RCC mets to?
MC to the lung via lymph and blood
but can also go to bone, regional nodes, adrenal gland, brain, opposite KD, adjacent organs and/or subQ tissue
what can RCC also cause?
paraneoplastic syndrome: tumor can secrete other biologically active products - adrenocorticotrophic hormones, enteroglucagon, PRL, insulin, gondatropins
can cause erythrocytosis, hypercalcemia, HTN, non-METs hepatic dysfxn
ssxs of RCC? sign in men?
the “great masquerader”
classic triad: gross hematuria, flank pain, palpable abd mass
fever, weight loss, HTN
in males: possible L varicocele from blockage of L testicular vein
ssxs of paraneoplastic syndromes
sxs of mets: dyspnea, cough, seizure, bone pn
labs of RCC? UA? first imaging? method of choice for staging and extent of brain mets? helpful to see mets? useful for vascular extension? to monitor tx response?
labs: elevated ESR, normochromic/normocytic anemia, low serum iron, low TIBC, abn LFT, possibly increased alpha-fetoprotein or beta-HCG
UA: gross or microscopic hematuria in 60% of cases
imaging: U/S shows simple cysts, tumor thrombus
CT is method of choice for staging and extent of brain mets
CXR can be helpful to mets
MRI useful for vascular extension
PET to monitor response to systemic tx
renal bx
tx and management of RCC?
1) Partial or Radical nephrectomy for localized stage I & II (<4cm tumor size)nGood evidence of efficacy: Coppin, et al. Cochrane database
2) Chemo and radiation —not proven effective (chemo has only 5% response rate)
3) Biologic response modulators, eg interleukin-2 therapy, interferon alpha
4) Molecularly Targeted Therapies: Inhibitors of VEGF: eg bevacizumab, sunitinib. Inhibitors of mTOR: eg temsirolimus, everolimis
5) Pre- and post-surgical support tissue healing nutrients, modified citrus pectin
6) Adjuvant naturopathic care—health, nutrition optimization. Consider referral to ND with FABNO credential
7) Stage-specific follow up with repeat CT
8) Note: Clinical trials underway for RCC vaccination: TroVax
prognosis of RCC?
5 yr survival for stage I is 91-100%
stage II is 74-96%
stage III is 59-70%
pts w/METs 16-32%
where does sarcoma of the KD arise from?
embryonic mesoderm thus why can also see sarcomas in bone, cartilage, fat, muscle, vasculature, blood
ssxs of renal sarcoma?
flank or abd pn, wt loss
types of renal sarcomas?
leiomyosarcoma, fibrosarcoma, liposarcoma, hemangiopericytomas, osteogenic sarcoma, malignant schwannomas
tx of renal sarcoma?
radical nephrectomy for localized dz is only effective therapy
adjuvant chemo reduces incidence of local recurrence in pts w/resectable retroperitoneal sarcomas
what is a nephroblastoma? MC in what population? age? MC in what ethnicity? MC u/l or b/l? comes from where?
Wilms’ Tumor
mixed malignant tumor of KD that is more commonly seen in children, MC 3-4 yo, MC in African Americans and those with FHx
most often U/L presentation
abn proliferation of metanephric lastema cells, genetic predisposition
ssxs of nephroblastoma?
abdominal swelling, abd pain, hypertension, N/V, constipation, loss of appetite, SOB
PE for nephroblastoma? UA and labs? dx? tx?
PE: abd mass, HTN UA: hematuria labs: anemia dx: found on US or CT tx: removal, possibly chemo if higher staged
condition commonly mistaken for RCC?
xanthogranulomatous pyelonephritis - uncommon form of chronic recurrent PN, usu from renal stone
May result from pyelonephritis or chronic obstruction. More common in diabetics and those who had urological instrumentation.
Clinical picture often previous PN that improves and then worsens,
75% of cases are e coli, but also Klebsiella, proteus, enterobacter
SSX: fever/chills, N/V, abdominal and flank pan
renal corticomedullary abscess
secondary renal tumors (METs to KDs) include CA from where?
20% lung
12% breast
11% stomach
9% contralateral KD
